CN101065125A - Imine compound - Google Patents

Imine compound Download PDF

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Publication number
CN101065125A
CN101065125A CNA2005800390054A CN200580039005A CN101065125A CN 101065125 A CN101065125 A CN 101065125A CN A2005800390054 A CNA2005800390054 A CN A2005800390054A CN 200580039005 A CN200580039005 A CN 200580039005A CN 101065125 A CN101065125 A CN 101065125A
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group
alkyl
expression
formula
halogen atom
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Chinese (zh)
Inventor
斋藤秀次
太田裕之
石坂知子
吉永光周
田续诚
横堀祐治
富岛保光
森田亚纪
户田喜久
德川纪美子
加来绫香
村上智美
吉村广光
关根伸吾
吉水孝绪
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Taisho Pharmaceutical Co Ltd
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Taisho Pharmaceutical Co Ltd
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Abstract

An imine compound represented by the formula (I) (wherein A represents a heterocyclic group; R<1>, R<2>, and R<3> each represents hydrogen, halogeno, C1-10 alkyl optionally substituted by haloaryl, C3-10 cycloalkyl, C1-6 haloalkyl, C1-10 alkoxy, etc.; R<4> represents optionally substituted C1-10 alkyl, C2-6 alkenyl, or aryl; R<5> represents hydrogen, C1-10 alkoxy, C1-6 haloalkyl, optionally substituted C1-10 alkyl or C2-6 alkenyl, optionally substituted aryl or heterocyclic group, etc.; and W represents -CO-, -CO-CO-, -CO-NH-, -CS-NH-, or -SO2-) or a cannabinoid receptor agonist containing the compound as an active ingredient. The imine compound has agonistic activity against a cannabinoid receptor and is useful as a therapeutic or preventive agent for pains and autoimmune diseases.

Description

Group with imine moiety
Technical field
The group with imine moiety of (cannabinoid) receptor agonism (excitation) that the present invention relates to have cannabinoid.
Background technology
Cannabinoid is to separate the material that obtains in nineteen sixty as the physiologically active ingredient of Fructus Cannabis, has analgesia, anxiety, calmness, causes effect such as sense of euphoria.Afterwards, by finding out its receptor, found that arachidonic ethanolamine (anandamide) etc. has the endogenous part of cannabinoid sample physiologically active.
As Cannabined receptor, nineteen ninety has been found cannabinoid 1 type (CB1) receptor, and known distribution is in central nervous system such as brain, and its agonist shows analgesic activity.Found cannabinoid 2 types (CB2) receptor in 1993, known distribution is in the immune tissue or cell that comprise blood cell line cells such as spleen, lymph node and leukocyte, B cell, T cell, macrophage, mastocyte, and its agonist shows immunosuppressive action, antiinflammatory action, analgesic activity etc.
As chemical compound with CB1 receptor agonism and chemical compound, for example be disclosed in non-patent literature 1 and 2 etc. with CB2 receptor agonism.
As with the group with imine moiety of The compounds of this invention structure proximate, for example be recorded in non-patent literature 3～8, the patent documentation 1～20 etc.As its purposes, reported the multiple use such as therapeutic agent, anti-allergic agent antiinflammatory immunomodulator, analgesics of the various inflammation that for example agricultural bactericide, herbicide, anticoagulant, leukocyte infiltration inhibition cause.But, do not have report with the Cannabined receptor agonism of group with imine moiety as effective ingredient.
[non-patent literature 1] Exp.Opin.Ther.Patent (2002) 12 (10): 1475-1489
[non-patent literature 2] Exp.Opin.Ther.Patent (2004) 14 (10): 1435-1452
[non-patent literature 3] European Journal of Medicinal Chmistry (1994) 29 (11): 841-854
[non-patent literature 4] Journal of Medicinal Chmistry (1966) 9 (1): 151-153
[non-patent literature 5] IzVestiya Akademii Nauk SSSR, SeriyaKimicheskaya (1953): 154-162
[non-patent literature 6] Farmaco, Edizione Scientifica (1985) 40 (3): 178-189
[non-patent literature 7] Journal of Heterocyclic Chemistry (1983) 20 (5): 1153-1154
[non-patent literature 8] Journal of Heterocyclic Chemistry (1981) 18 (4): 745-750
[patent documentation 1] WO9215564
[patent documentation 2] EP432600
[patent documentation 3] DE1036326
[patent documentation 4] WO2001055139
[patent documentation 5] WO2000063207
[patent documentation 6] JP2003292485
[patent documentation 7] WO2002002542
[patent documentation 8] WO2003097605
[patent documentation 9] JP2003192591
[patent documentation 10] WO2000017196
[patent documentation 11] WO9842703
[patent documentation 12] WO2002002542
[patent documentation 13] JP02250874
[patent documentation 14] JP62004277
[patent documentation 15] EP40573
[patent documentation 16] JP63203672
[patent documentation 17] JP08081449
[patent documentation 18] WO9703058
[patent documentation 19] WO9404516
[patent documentation 20] JP02229164
Summary of the invention
The object of the present invention is to provide a kind of novel group with imine moiety with Cannabined receptor agonism.
The inventor has carried out concentrated research to group with imine moiety, found that the novel group with imine moiety with Cannabined receptor agonism, thereby has finished the present invention.
The present invention below is described.
The invention provides the Cannabined receptor excitomotor that group with imine moiety or its officinal salt with formula (I) expression are effective ingredient.
[changing 1]
[in the formula, A represents any one ring (in the formula, X represents oxygen atom or sulphur atom, X ' expression CH or nitrogen-atoms) of following various expression,
[changing 2]
Figure A20058003900500482
R 1Expression
Hydrogen atom;
Halogen atom;
Can be by the C of " halogen atom substituted aryl " replacement 1-10Alkyl;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression; Perhaps
C can be selected from 1-6Alkyl, C 1-6The aryl that 1～3 group of haloalkyl and halogen atom replaces,
R 2And R 3Expression respectively
Hydrogen atom;
Halogen atom;
C 1-6Alkyl;
C 1-6Haloalkyl; Perhaps
C can be selected from 1-6Alkyl, C 1-6The aryl that 1～3 group of haloalkyl and halogen atom replaces,
R 4Expression
C 1-10Alkyl;
C 1-6Haloalkyl;
By C 3-10Cycloalkyl, C 1-6Alkoxyl, hydroxyl, amino, phthaloyl imino, cyano group, arylthio, C 2-6Alkoxy carbonyl, carboxyl, formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression or can be by " C 1-6Haloalkyl, C 2-6Alkoxy carbonyl, carboxyl or N-piperidino carbamoyl " C that replaces of the aryl that replaces 1-10Alkyl or C 2-6Thiazolinyl;
C 2-6Haloalkenyl group;
C 2-6Alkynyl;
1,1-dioxo tetrahydro-thienyl;
Or aryl,
R 5Expression
Hydrogen atom;
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, C 1-6Haloalkyl, can be by " C 1-6Alkoxyl or aryl " C that replaces 1-6Alkoxyl, can be by 1～2 C 1-6The C that alkyl replaces 3-10Cycloalkyloxy, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl, C 1-6Halogenated alkoxy, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, phthaloyl imino, C 1-6Alkanoyloxy, aralkoxy, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group in the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkyl, C 1-6Alkoxyl, C 2-6Alkoxy carbonyl, C 1-6Haloalkyl or C 1-6The aryloxy group that halogenated alkoxy replaces;
Aralkoxy;
The group of formula (II) expression,
[changing 3]
Figure A20058003900500501
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
Fluorenyl;
Phthaloyl imino;
2-oxo-pyrrolidine base;
The group of formula (III) expression;
[changing 4]
Figure A20058003900500511
(in the formula, n represents 0 or 1.)
The perhaps group of formula (IV) expression;
[changing 5]
Figure A20058003900500512
(in the formula, Y represents-(CH 2) p-,-CO-CH 2-CH 2-,-CO-CH 2-CH 2-CH 2-,-O-CH 2-CH 2-,-O-CH 2-CH=CH-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer)
R 55Expression
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Can be by C 1-6The aryl sulfonyl that alkyl or halogen atom replace;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl, cyano group and nitro replaces;
Can be by C 1-6Alkyl or C 1-6The heterocyclic group that haloalkyl replaces;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 63) R 73(in the formula, R 63And R 73Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Hydroxy alkyl, C 1-6Alkoxy C 1-6Alkyl, aryl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl, benzoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 1-6Alkanoyloxy;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 2-6The alkyl halide acyl group;
Carboxyl;
C 2-6Alkoxy carbonyl;
The C that can be replaced by aryl 2-6Cyclic amino;
Formula-CON (R 64) R 74(in the formula, R 64And R 74Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkoxy C 1-6Alkyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-SO 2N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
C 1-6Alkyl sulphinyl;
The C that can be replaced by halogen atom 1-6Alkyl sulphonyl; Perhaps
The aryl sulfonyl that can be replaced by halogen atom,
R 56Expression
Hydrogen atom;
Halogen atom;
Can by: can be by " C 1-6Alkyl or halogen atom " C that replaces of the aryl, pyridine radicals, thienyl or the heterocyclic group that replace 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl;
C 1-10Alkoxyl;
C 2-6Thiazolinyl;
C can be selected from 1-6Alkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
C 1-6Alkanoyl;
C 1-6Alkyl sulphinyl;
C 1-6Alkyl sulphonyl;
The aryl sulfonyl that can be replaced by halogen atom;
Hydroxyl;
Cyano group; Perhaps
Nitro,
R 57Expression
Hydrogen atom;
Can be by the C of " pyridine radicals or thienyl " replacement 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl;
Halogen atom;
C 2-6Thiazolinyl;
The aryl that can be replaced by halogen atom;
C 1-10Alkoxyl;
C 1-6Alkanoyl; Perhaps
C 1-6Alkyl sulphinyl,
M represents 1～3 integer }
A and b represent 0 or 1 respectively,
W represents-CO-,-CO-CO-,-CO-NH-,-CS-NH-or-SO 2-.]
Other modes of the present invention provide with the group with imine moiety of following formula (I-1) expression or its officinal salt Cannabined receptor excitomotor as effective ingredient.
[changing 6]
Figure A20058003900500541
[in the formula, A 1Any one ring (in the formula, X represents oxygen atom or sulphur atom) of representing following various expression,
[changing 7]
Figure A20058003900500551
R 11Expression
Hydrogen atom;
Halogen atom;
C 1-6Alkyl;
C 2-6Thiazolinyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl; Perhaps
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 21And R 31Expression respectively
Hydrogen atom;
Halogen atom; Perhaps
C 1-6Alkyl,
R 41Expression
Can be by halogen atom, C 3-10Cycloalkyl, aryl or C 1-6The C that alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl,
R 51Expression
C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl and halogen atom " the aryl that replaces of 1～5 group or the C that replaces of 1～3 group of aryloxy group and heterocyclic group 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-1) expression,
[changing 8]
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
Fluorenyl; Perhaps
The group of formula (IV-1) expression,
[changing 9]
Figure A20058003900500562
(in the formula, Y 1Expression-(CH 2) p-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer)
R 551And R 561Expression respectively
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 634) R 734(in the formula, R 634And R 734Represent hydrogen atom, C respectively 1-6Alkyl, aryl or C 1-6Alkanoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group;
C 1-6Alkyl sulphonyl; Perhaps
The aryl sulfonyl that can be replaced by halogen atom,
R 571Expression
Hydrogen atom;
C 1-10Alkyl;
C 1-10Alkoxyl; Perhaps
Halogen atom,
M represents 1～3 integer }, a and b represent 0 or 1 respectively, W represents CO or SO 2]
Other modes of the present invention provide group with imine moiety or its officinal salt of following formula (I-1) expression.
[changing 10]
Figure A20058003900500581
[in the formula, A 1Any one ring (in the formula, X represents oxygen atom or sulphur atom) of representing following various expression,
[changing 11]
Figure A20058003900500591
R 11Expression
Hydrogen atom;
Halogen atom;
C 1-6Alkyl;
C 2-6Thiazolinyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl; Perhaps
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 21And R 31Expression respectively
Hydrogen atom;
Halogen atom; Perhaps
C 1-6Alkyl,
R 41Expression
Can be by halogen atom, C 3-10Cycloalkyl, aryl or C 1-6The C that alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl,
R 51Expression
C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl and halogen atom " the aryl that replaces of 1～5 group or the C that replaces of 1～3 group of aryloxy group and heterocyclic group 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-1) expression,
[changing 12]
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
Fluorenyl; Perhaps
The group of formula (IV-1) expression,
[changing 13]
(in the formula, Y 1Expression-(CH 2) p-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer)
R 551And R 561Expression respectively
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 634) R 734(in the formula, R 634And R 734Represent hydrogen atom, C respectively 1-6Alkyl, aryl or C 1-6Alkanoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group;
C 1-6Alkyl sulphonyl; Perhaps
The aryl sulfonyl that can be replaced by halogen atom,
R 571Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl,
M represents 1～3 integer }, a and b represent 0 or 1 respectively, W represents CO or SO 2]
Other modes of the present invention provide with the group with imine moiety of formula (I-2) expression or its officinal salt Cannabined receptor excitomotor as effective ingredient.
[changing 14]
[in the formula, R 12And R 22Expression respectively
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Can be by the aryl of 1～3 halogen atom replacement; Perhaps
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression, perhaps represent R 11And R 22Connecting together with adjacent carbon atom, form can be by C 1-6The group of phenyl ring, pyridine ring or cyclohexene ring that alkyl or halogen atom replace,
R 42Expression
Can be by halogen atom, cyano group, carboxyl, C 2-6Alkoxy carbonyl, C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl, C 1-6Halogenated alkoxy, C 1-6Halogenated alkylthio, carboxyl, C 2-6Alkoxy carbonyl or piperidino carbamoyl " aryl, arylthio, the C that replace 1-6Alkoxyl or formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl or C 2-6Thiazolinyl; Perhaps
C 2-6Alkynyl,
R 52Expression
Hydrogen atom;
C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, can be by " C 1-6Alkoxyl or aryl " C that replaces 1-6Alkoxyl, can be by C 1-6The C that alkyl replaces 3-10Cycloalkyloxy, " C can be selected from 1-6Alkyl, C 1-6Haloalkyl, C 1-6Alkoxyl, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, phthaloyl imino, C 1-6Alkanoyloxy, aralkoxy, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group of the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkyl, C 1-6Alkoxyl, C 2-6Alkoxy carbonyl or C 1-6The aryloxy group that haloalkyl replaces;
Aralkoxy;
The group of formula (II-2) expression,
[changing 15]
Figure A20058003900500631
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
Fluorenyl;
2-oxo-pyrrolidine base;
The group of formula (III) expression;
[changing 16]
(in the formula, n represents 0 or 1)
The perhaps group of formula (IV-2) expression,
[changing 17]
Figure A20058003900500642
(in the formula, Y 2Expression-(CH 2) p-,-CO-CH 2-CH 2-,-O-CH 2-CH=CH-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer),
R 552Expression
Hydrogen atom;
Halogen atom;
Can be by aryl, aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Can be by C 1-6The arylthio that alkyl or halogen atom replace;
Can be by C 1-6The aryl sulfonyl that alkyl or halogen atom replace;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6Alkyl or C 1-6The heterocyclic group that haloalkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 63) R 73(in the formula, R 63And R 73Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Hydroxy alkyl, C 1-6Alkoxy C 1-6Alkyl, aryl, C 1-6Alkanoyl or benzoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
Carboxyl;
C 2-6Alkoxy carbonyl;
Can be by the C of aralkyl or aryl replacement 2-6Cyclic amino;
Formula-CON (R 64) R 74(in the formula, R 64And R 74Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkoxy C 1-6Alkyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-SO 2N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
The C that can be replaced by halogen atom 1-6Alkyl sulphonyl;
The aryl sulfonyl that can be replaced by halogen atom; Perhaps
2-oxa--3-oxo bicyclo-[2.2.1] heptyl,
R 562Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-6Alkoxyl,
R 572Expression
Hydrogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
Halogen atom; Perhaps
C 1-6Alkoxyl,
M represents 1～3 integer }, X represents oxygen atom or sulphur atom, W represents CO or SO 2]
Other modes of the present invention provide group with imine moiety or its officinal salt,
Wherein, in the following formula (I-2),
[changing 18]
Figure A20058003900500661
W is CO,
R 12For
Halogen atom;
C 1-6Alkyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Can be by the aryl of 1～3 halogen atom replacement; Perhaps
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 22For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Or
Aryl, perhaps R 12And R 22Connecting together with adjacent carbon atom, form can be by C 1-6The group of phenyl ring, pyridine ring or cyclohexene ring that alkyl or halogen atom replace,
R 42Be C 3-10Cycloalkyl or C 1-6The C that alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl,
X and R 52Identical with above-mentioned implication.
Other modes of the present invention provide with the group with imine moiety of formula (I-3) expression or its officinal salt Cannabined receptor excitomotor as effective ingredient.
[changing 19]
Figure A20058003900500671
[in the formula, dotted line is represented one of any two keys that are,
X 3Expression C (R 13), S or O,
R 13, R 23And R 33Expression respectively
Hydrogen atom;
The C that can be replaced by the halogen atom substituted aryl 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl; Or
Can be by the aryl or aralkyl of 1～3 halogen atom replacement, perhaps X 3Be C (R 13) time, R 13With R 23Expression-CH connects together 2-S-CH 2Group (wherein, the X of-expression 3During for S or O, R 33Be not substituted),
R 43Expression
1,1-dioxo tetrahydro-thienyl;
C can be selected from 3-10Cycloalkyl, C 1-6Haloalkyl and C 1-6The C that the group of alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl; Perhaps aryl,
R 53Expression
Hydrogen atom;
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, " C can be selected from 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkanoyloxy, aralkoxy and C 1-6The C that 1～3 group of alkylthio group replaces 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-3) expression,
[changing 20]
Figure A20058003900500681
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
The group of formula (III) expression;
[changing 21]
(in the formula, N represents 0 or 1.)
The perhaps group of formula (IV-3) expression,
[changing 22]
Figure A20058003900500692
(in the formula, Y 3Expression-O-CH 2-CH=CH-or-O-(CH 2) q-O-, q represents 1～3 integer)
R 553Expression
Hydrogen atom;
Halogen atom;
Aryl;
C 1-10Alkyl;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
Can be by the aryl of 1～3 halogen atom or cyano group replacement;
Heterocyclic group;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 633) R 733(in the formula, R 633And R 733Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Cyano group;
Nitro;
C 2-6Alkoxy carbonyl;
R 563Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Haloalkyl,
R 573Expression
Hydrogen atom;
C 1-10Alkyl;
Halogen atom; Perhaps
C 1-10Alkoxyl,
M represents 1～3 integer }, W represents-CO-,-CO-CO-,-CO-NH-,-CS-NH-or-SO 2-.]
Other modes of the present invention provide group with imine moiety or its officinal salt of formula (I-3) expression.
[changing 23]
Figure A20058003900500701
[in the formula, dotted line one of represents arbitrarily to be two keys,
X 3Expression C (R 13), S or O,
R 13, R 23And R 33Expression respectively
Hydrogen atom;
The C that can be replaced by the halogen atom substituted aryl 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl; Or
Can be by the aryl or aralkyl of 1～3 halogen atom replacement, perhaps X 3Be C (R 13) time, R 13With R 23Expression-CH connects together 2-S-CH 2Group (wherein, the X of-expression 3During for S or O, R 33Be not substituted),
R 43Expression
1,1-dioxo tetrahydro-thienyl;
C can be selected from 3-10Cycloalkyl, C 1-6Haloalkyl and C 1-6The C that the group of alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl; Perhaps aryl,
R 53Expression
Hydrogen atom;
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, " C can be selected from 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkanoyloxy, aralkoxy and C 1-6The C that 1～3 group of alkylthio group replaces 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-3) expression,
[changing 24]
Figure A20058003900500711
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
The group of formula (III) expression;
[changing 25]
Figure A20058003900500721
(in the formula, n represents 0 or 1)
The perhaps group of formula (IV-3) expression,
[changing 26]
Figure A20058003900500722
(in the formula, Y 3Expression-O-CH 2-CH=CH-or-O-(CH 2) q-O-, q represents 1～3 integer)
R 553Expression
Hydrogen atom;
Halogen atom;
Aryl;
C 1-10Alkyl;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
Can be by the aryl of 1～3 halogen atom or cyano group replacement;
Heterocyclic group;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 633) R 733(in the formula, R 633And R 733Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Cyano group;
Nitro;
C 2-6Alkoxy carbonyl;
R 563Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Haloalkyl,
R 573Expression
Hydrogen atom;
C 1-10Alkyl;
Halogen atom; Perhaps
C 1-10Alkoxyl,
M represents 1～3 integer }, W represents-CO-,-CO-CO-,-CO-NH-,-CS-NH-or-SO 2-.]
Among the present invention, R 4, R 41, R 42Or R 43Preferred C 2-6Thiazolinyl or quilt " C 3-10Cycloalkyl or C 1-10Alkoxyl " C that replaces 1-10Alkyl, more preferably C 3-10The C of cycloalkyl substituted 1-10Alkyl.
In addition, among the present invention, preferred R 5, R 51, R 52Or R 53For being selected from C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl and halogen atom " C that replaces of 1～3 group in the aryl, thienyl, halogen atom and the aryloxy group that replace 1-10Alkyl or C 2-6Thiazolinyl, perhaps formula (II), (II-1), (II-2) or (II-3) group of expression, R 55, R 551, R 552Or R 553Be hydrogen atom; Halogen atom; C 1-10Alkyl; C 1-6Haloalkyl; C 1-10Alkoxyl; C 1-6Halogenated alkoxy; C 3-10Cycloalkyl; Aryl; Can be by C 1-6The heterocyclic group that alkyl replaces; Aryloxy group; Morpholinyl; Arylamino; Cyano group; C 1-6Alkanoyl; C 2-6The alkyl halide acyl group; Perhaps C 1-6Alkyl sulphonyl, R 56, R 561, R 562Or R 563Be hydrogen atom; Halogen atom; C 1-6Haloalkyl; Perhaps C 1-6Alkoxyl, R 57, R 571, R 572Or R 573Be hydrogen atom; Halogen atom; C 1-10Alkyl or C 1-10The chemical compound of alkoxyl.
More preferably R 5, R 51, R 52Or R 53The group that is respectively formula (II), (II-1), (II-2) or (II-3) represents, B is a phenyl, R 55, R 551, R 552Or R 553Be halogen atom; C 1-6Alkyl; C 1-6Haloalkyl; C 1-6Alkoxyl; C 1-6Halogenated alkoxy; C 3-8Cycloalkyl; Aryl; Aryloxy group; Morpholinyl; Arylamino; Cyano group; C 1-6Alkanoyl; C 2-6The alkyl halide acyl group; Or C 1-6Alkyl sulphonyl, R 56, R 561, R 562Or R 563Be hydrogen atom; Halogen atom; C 1-6Haloalkyl; Or C 1-6Alkoxyl, R 57, R 571, R 572Or R 573Be hydrogen atom; Halogen atom; C 1-6Alkyl or C 1-6Alkoxyl, m are 1 chemical compound, most preferably R 5, R 51, R 52Or R 53For being selected from halogen atom, C 1-6Alkyl, C 1-6Haloalkyl, C 1-6Alkoxyl, cyano group and C 1-6The chemical compound of the phenyl that 1～3 group in the halogenated alkoxy replaces.
In addition, formula (I) (I-1) (I-2) and (I-3) in, the spatial configuration of two keys that the carbon atom of the group that＞C=N-CO-represents and nitrogen-atoms form is (Z) configuration preferably.
In addition, also comprise its prodrug, hydrate, solvate in the group with imine moiety of the present invention.
The implication of each term that uses in this description below is described.
In the present invention, " C X-Y" be meant that the group that is connected on thereafter has X～Y carbon atom.
" halogen atom " is fluorine, chlorine, bromine or iodine.
" C 1-6Alkyl " be the alkyl of 1～6 of straight chain shape or catenate carbon number; can exemplified by methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, 2-butyl, the tert-butyl group, 1; 1-dimethyl ethyl, n-pentyl, isopentyl, 1,1-dimethyl propyl, n-hexyl etc.
" C 1-10Alkyl " be straight chain shape or the alkyl that props up 1～10 of catenate carbon number, remove above-mentioned " C 1-6Alkyl " instantiation beyond, can also exemplify 1,1,3,3-tetramethyl butyl, n-nonyl, positive decyl etc.
" C 1-6Haloalkyl " be above-mentioned " C 1-6Alkyl " alkyl that replaced by one or more halogen atoms; can exemplify methyl fluoride, difluoromethyl, trifluoromethyl, 2; 2; 2-trifluoroethyl, 2; 2; 2-three chloroethyls, pentafluoroethyl group, 3,3,3-trifluoro propyl, perfluoro propyl, 4-fluorine butyl, 4-chlorobutyl, 4-brombutyl, perfluoro hexyl etc.
" C 1-6Alkoxyl " be straight chain shape or the alkoxyl that props up 1～6 of catenate carbon numbers, can exemplify methoxyl group, ethyoxyl, 1-propoxyl group, isopropoxy, 1-butoxy, 1-methyl isophthalic acid-propoxyl group, tert-butoxy, 1-amoxy etc.
" C 1-10Alkoxyl " be straight chain shape or the alkoxyl that props up 1～10 of catenate carbon number, remove above-mentioned " C 1-6Alkoxyl " instantiation beyond, can also exemplify 1,1,3,3-tetramethyl butoxy, n-decyloxy etc.
" aryl " is the aromatic carbon ring group of the monocycle～4 yuan ring of 6～18 of carbon numbers, can exemplified by phenyl, naphthyl, anthryl (anthoryl), phenanthryl, naphthacenyl, pyrenyl etc.Preferred phenyl.
" C 3-10Cycloalkyl " be the cycloalkyl of 3～10 of carbon numbers, can exemplify cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl, suberyl, adamantyl etc.
" C 2-6Thiazolinyl " have an alkyl of 2～6 of the straight chain shape of two keys more than 1 or catenate carbon numbers for the optional position of above-mentioned " alkyl "; can exemplified by vinyl, 1-acrylic, 2-acrylic, crotyl, 1,3-butadiene base, pentenyl, 3-pentenyl, 2-hexenyl etc.
" C 2-6Alkynyl " be meant and the alkynyl of straight or branched can exemplify acetenyl, 1-propinyl, 2-propynyl etc. with 2～6 of carbon numbers.
" C 2-6Alkoxy carbonyl " be meant that above-mentioned alkoxyl combines the group that obtains with carbonyl, can exemplify methoxycarbonyl, ethoxy carbonyl, tert-butoxycarbonyl etc.
" hydroxyl C 1-6Alkyl " be meant that 1～2 hydroxyl replaces the above-mentioned C that obtains 1-6Alkyl can exemplify methylol, 2-ethoxy, 4-hydroxyl butyl etc.
" cyclic amino " can exemplify pyrrolidinyl, piperidino, piperazinyl, morpholinyl, thio-morpholinyl etc. for having the cyclic amino of 2～6 of carbon numbers.In the thio-morpholinyl, the dioxide of sulphur atom is also included among the present invention.
" C 1-6Halogenated alkoxy " be above-mentioned " C 1-6Alkoxyl " alkoxyl that replaced by one or more halogen atoms; can exemplify fluorine methoxyl group, difluoro-methoxy, trifluoromethoxy, 2; 2; 2-trifluoro ethoxy, 2; 2,2-three chloroethoxies, five fluorine ethyoxyls, perfluor propoxyl group, 4-fluorine butoxy, 4-chlorine butoxy, 4-bromine butoxy, perfluor hexyloxy etc.
" C 1-6Alkylthio group " be the alkylthio group of 1～6 of straight chain shape or catenate carbon number; can exemplify methyl mercapto, ethylmercapto group, positive rosickyite base, iprotiazem base, positive butylthio, 2-butylthio, uncle's butylthio, 1; 1-dimethyl ethylmercapto group, positive penta sulfenyl, isoamyl sulfenyl, 1,1-dimethyl propylene sulfenyl, own sulfenyl etc. just.
" C 1-6Halogenated alkylthio " be above-mentioned " C 1-6Alkylthio group " alkylthio group that replaced by one or more halogen atoms; can exemplify fluorine methyl mercapto, difluoro methyl mercapto, trifluoromethylthio, 2; 2; 2-trifluoro ethylmercapto group, 2; 2,2-trichlorine ethylmercapto group, five fluorine ethylmercapto groups, 4-fluorine butylthio, 4-neoprene sulfenyl, 4-bromine butylthio, the own sulfenyl of perfluor etc.
" arylthio " can exemplify thiophenyl, naphthalene sulfenyl etc.
" C 2-6Alkenylthio group " be straight chain shape or the alkenylthio group that props up 2～6 of catenate carbon numbers, can exemplify ethylene sulfenyl, 1-propylene sulfenyl, 2-propylene sulfenyl, 2-butylene sulfenyl, 1,3-butadiene sulfenyl, 2-amylene sulfenyl, 3-amylene sulfenyl, 2-hexene sulfenyl etc.
" C 1-6Alkanoyl " be straight chain shape or the alkanoyl that props up 1～6 of catenate carbon numbers, can exemplify formoxyl, acetyl group, propiono, different propiono, bytyry, valeryl etc.
" C 1-6Alkanoyloxy " be meant above-mentioned C 1-6Alkanoyl combines the group that obtains with the oxygen base, can exemplify acetoxyl group, propionyloxy, new pentane acyloxy etc.
" C 1-6Alkanoyloxy C 1-6Alkyl " be meant above-mentioned C 1-6Alkanoyloxy and C 1-6Alkyl can exemplify acetoxyl group ethyl, propionyloxy methyl, oxy acid methyl neopentyl etc. in conjunction with the group that obtains.
" C 2-6The alkyl halide acyl group " be " C 2-6Alkanoyl " by the alkanoyl that halogen atom replaces, can exemplify acetyl fluoride base, trifluoroacetyl group, 2,2,2-trifluoropropyl acyl group, 2,2,2-trichlorine propiono, 4-fluorine bytyry, 4-chlorobutyryl, 4-bromine bytyry etc.
" C 1-6Alkoxy C 1-6Alkoxyl " be meant 2 C 1-6Alkoxyl is in conjunction with the group that obtains, can exemplify methoxymethoxy, methoxy propoxy, ethyoxyl propoxyl group, heptan oxygen base oxethyl etc.
" C 1-6Alkoxy C 1-6Alkyl " be meant C 1-6Alkoxyl and C 1-6Alkyl is in conjunction with the group that obtains, can exemplify methoxy, methoxy-propyl, ethoxycarbonyl propyl, heptan oxygen base ethyl etc.
" aryloxy group " can exemplify phenoxy group, naphthoxy etc. for the group that above-mentioned " aryl " replaces by oxygen atom.
" aralkyl " is meant that aryl combines the group that obtains with alkyl, can exemplify benzyl, phenethyl, menaphthyl etc.
" aralkoxy " is meant that aralkyl combines the group that obtains with the oxygen base, can exemplify benzyloxy, benzene ethyoxyl, naphthalene methoxyl group etc.
" heterocyclic group " for contain be selected from nitrogen-atoms, oxygen atom and sulphur atom 1～3 atom as monocyclic type heteroaromatic group that becomes annular atoms or thick and heterocyclic group, comprise that also saturated heterocyclic group, aromatic heterocyclic group and aromatic heterocyclic group have the monocyclic condensed ring formula of fractional saturation heterocyclic group.In addition, having the monocyclic condensed ring formula of fractional saturation heterocyclic group can be replaced by=O.Preferred its ring of this heterocyclic group has the heterocycle of 5～10 atoms.
As the saturated heterocyclic group, can exemplify azacyclopropane base, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxolanyl base, thiolanyl base, piperidyl, piperazinyl, morpholinyl etc.
As aromatic heterocyclic group, can exemplify pyridine radicals, pyridazinyl, pyrimidine radicals, pyrazinyl, quinolyl, isoquinolyl, thienyl (for example, 2-thienyl, the 3-thienyl), pyrrole radicals (for example, the 1-pyrrole radicals, the 2-pyrrole radicals, the 3-pyrrole radicals), thiazolyl (for example, 2-thiazolyl, the 4-thiazolyl, the 5-thiazolyl), isothiazolyl (for example, 3-isothiazolyl, the 4-isothiazolyl, the 5-isothiazolyl), pyrazolyl (for example, the 1-pyrazolyl, the 3-pyrazolyl, the 4-pyrazolyl), imidazole radicals (for example, the 1-imidazole radicals, the 2-imidazole radicals, the 3-imidazole radicals), furyl (for example, 2-furyl, the 3-furyl),  azoles base (for example, 2- azoles base, 4- azoles base, 5- azoles base), different  azoles base (for example, the different  azoles of 3-base, the different  azoles of 4-base, the different  azoles of 5-base), the  di azoly (for example, 1,2,3- di azoly, 1,3,4- di azoly), thiadiazolyl group (for example, 1,2, the 3-thiadiazolyl group, 1,3, the 4-thiadiazolyl group), triazolyl (for example, 1,2, the 4-triazolyl), benzofuranyl (for example, 2-benzofuranyl, the 3-benzofuranyl, the 4-benzofuranyl, the 5-benzofuranyl), benzothienyl (for example, 2-benzothienyl, the 3-benzothienyl, the 4-benzothienyl, the 5-benzothienyl), indyl (for example, the 2-indyl, the 3-indyl, the 4-indyl, the 5-indyl), the benzoxazol base (for example, 2-benzoxazol base, 4-benzoxazol base, 5-benzoxazol base, 6-benzoxazol base), benzisoxa  azoles base (for example, the different  azoles of 3-benzo [c] base, the different  azoles of 4-benzo [c] base, the different  azoles of 5-benzo [c] base, the different  azoles of 6-benzo [c] base, the different  azoles of 3-benzo [d] base, the different  azoles of 4-benzo [d] base, the different  azoles of 5-benzo [d] base, the different  azoles of 6-benzo [d] base), indazolyl (for example, 3-indazolyl, the 4-indazolyl, the 5-indazolyl, the 6-indazolyl), benzimidazolyl (for example, the 2-benzimidazolyl, the 4-benzimidazolyl, the 5-benzimidazolyl, the 6-benzimidazolyl), benzo  di azoly (for example, 4-benzo [1,2,5]  di azoly, 5-benzo [1,2,5]  di azoly, 4-benzo [1,2,3]  di azoly, 5-benzo [1,2,3]  di azoly), diazosulfide base (for example, 4-benzo [1,2,5] thiadiazolyl group, 5-benzo [1,2,5] thiadiazolyl group, 4-benzo [1,2,3] thiadiazolyl group, 5-benzo [1,2,3] thiadiazolyl group), indolizine base (indolidinyl) (for example, 1-indolizine base, 2-indolizine base, 3-indolizine base, 5-indolizine base), the thienopyridine base (for example, 2-thieno [2,3-b] pyridine radicals, 3-thieno [2,3-b] pyridine radicals, 5-thieno [2,3-b] pyridine radicals, 6-thieno [2,3-b] pyridine radicals, 2-thieno [3,2-b] pyridine radicals, 3-thieno [3,2-b] pyridine radicals, 5-thieno [3,2-b] pyridine radicals, 6-thieno [3,2-b] pyridine radicals), the Pyrazolopyridine base (for example, 2-Pyrazolopyridine base, 3-Pyrazolopyridine base, 5-Pyrazolopyridine base, 6-Pyrazolopyridine base), imidazopyridyl (for example, 1-imidazo [1,5-a] pyridine radicals, 3-imidazo [1,5-a] pyridine radicals, 5-imidazo [1,5-a] pyridine radicals, 7-imidazo [1,5-a] pyridine radicals, 2-imidazo [1,2-a] pyridine radicals, 3-imidazo [1,2-a] pyridine radicals, 5-imidazo [1,2-a] pyridine radicals, 7-imidazo [1,2-a] pyridine radicals), (for example, the 1-imidazo [1 for the Imidazopyrazines base, 5-a] pyrazinyl, 3-imidazo [1,5-a] pyrazinyl, 5-imidazo [1,5-a] pyrazinyl, 8-imidazo [1,5-a] pyrazinyl, 2-imidazo [1,2-a] pyrazinyl, 3-imidazo [1,2-a] pyrazinyl, 5-imidazo [1,2-a] pyrazinyl, 8-imidazo [1,2-a] pyrazinyl), the pyrazolopyrimidine base (for example, 2-pyrazolo [1,5-a] pyrimidine radicals, 3-pyrazolo [1,5-a] pyrimidine radicals, 5-pyrazolo [1,5-a] pyrimidine radicals, 6-pyrazolo [1,5-a] pyrimidine radicals, 2-pyrazolo [1,5-c] pyrimidine radicals, 3-pyrazolo [1,5-c] pyrimidine radicals, 4-pyrazolo [1,5-c] pyrimidine radicals, 5-pyrazolo [1,5-c] pyrimidine radicals), triazolopyrimidinyl (for example, 3-[1,2,3] triazol [1,5-a] pyrimidine radicals, 5-[1,2,3] triazol [1,5-a] pyrimidine radicals, 6-[1,2,3] triazol [1,5-a] pyrimidine radicals, 3-[1,2,3] triazol [1,5-c] pyrimidine radicals, 4-[1,2,3] triazol [1,5-c] pyrimidine radicals, 5-[1,2,3] triazol [1,5-c] pyrimidine radicals, 2-[1,2,41 triazols [1,5-a] pyrimidine radicals, 5-[1,2,4] triazol [1,5-a] pyrimidine radicals, 6-[1,2,4] triazol [1,5-a] pyrimidine radicals, 7-[1,2,4] triazol [1,5-a] pyrimidine radicals, 2-[1,2,4] triazol [1,5-c] pyrimidine radicals, 5-[1,2,4] triazol [1,5-c] pyrimidine radicals, 7-[1,2,4] triazol [1,5-c] pyrimidine radicals, 8-[1,2,4] triazol [1,5-c] pyrimidine radicals), the thienothiophene base (for example, 2-thieno [2,3-b] thienyl, 3-thieno [2,3-b] thienyl, 2-thieno [3,2-b] thienyl, 3-thieno [3,2-b] thienyl), the Imidazothiazole base (for example, 2-imidazo [2,1-b] thiazolyl, 3-imidazo [2,1-b] thiazolyl, 5-imidazo [2,1-b] thiazolyl, 2-imidazo [5,1-b] thiazolyl, 3-imidazo [5,1-b] thiazolyl, 5-imidazo [5,1-b] thiazolyl) etc.
Has the monocyclic condensed ring formula of fractional saturation heterocyclic group as aromatic heterocyclic group, can exemplify the tetrahydrochysene benzfuran base, the tetrahydro benzo thienyl, the tetrahydro benzo pyrrole radicals, 2,3-dihydro-1H-benzofuranyl, 2,3-dihydro-1H-benzothienyl, 2,3-dihydro-1H-indyl, 2,3-dihydro-1H-indazolyl, 2,3-dihydro-1H-benzotriazole base, 2,3-dihydro-1H-benzoxazolyl, 2,3-dihydro-1H-benzothiazolyl, benzo [1,3] oxathiolyl base, benzo [1,3] dioxolyl (dioxolyl), the 2H-chromenyl, Chromanyl, indolinyl, iso-dihydro-indole-group etc.
Monocycle with fractional saturation, the condensed ring formula heterocyclic group that quilt=O replaces can exemplify 2-oxo-1,3-dihydro-1H-indole basic ring, 3-oxo-1,2-two-hydrogen-1H-indazole basic ring, 2-oxo-3H-benzoxazole basic ring, 2-oxo-3H-benzothiazole basic ring, 2-oxo-benzo [1,3] oxathiolyl basic ring, 2-oxo-benzo [1,3] dioxolyl ring, 2-oxo-chromene basic ring etc.
As the heterocyclic group of B ring, preferred pyridine radicals, pyridazinyl, pyrimidine radicals, pyrazinyl, quinolyl and isoquinolyl.
" C 1-6Alkyl sulphinyl " be above-mentioned " C 1-6Alkyl " group that replaces by SO, can the exemplified by methyl sulfinyl, ethyl sulfinyl, n-pro-pyl sulfinyl, normal-butyl sulfinyl, tert-butyl group sulfinyl, n-pentyl sulfinyl etc.
" the C that can be replaced by halogen atom 1-6Alkyl sulphonyl " be above-mentioned " C 1-6Alkyl " or above-mentioned " C 1-6Haloalkyl " group that replaces by sulfonyl; can the exemplified by methyl sulfonyl, ethylsulfonyl, n-pro-pyl sulfonyl, normal-butyl sulfonyl, tert-butyl group sulfonyl, n-pentyl sulfonyl, methyl fluoride sulfonyl, difluoromethyl sulfonyl, trifluoromethyl sulfonyl, 2; 2; 2-trifluoroethyl sulfonyl, 2; 2,2-trichlorine ethylsulfonyl, pentafluoroethyl group sulfonyl, 4-fluorine butyl sulfonyl, 4-chlorobutyl sulfonyl, 4-brombutyl sulfonyl etc.
" aryl sulfonyl that can be replaced by halogen atom " is the sulfonyl that above-mentioned aryl can be replaced by halogen atom; can exemplify benzenesulfonyl, 4-chlorobenzene sulfonyl, 4-fluorobenzene sulfonyl, 2; 4-dibromobenzene sulfonyl, 2,4 difluorobenzene sulfonyl, naphthalene sulfonyl base, 6-bromonaphthalene sulfonyl etc.
" prodrug " is meant hydrolysis in vivo, and regeneration has the chemical compound of the group with imine moiety of Cannabined receptor agonism.
" officinal salt " is acid-addition salts and base addition salts, as acid-addition salts, can exemplify inorganic acid salts such as hydrochlorate, hydrobromate, sulfate, acylates such as citrate, oxalates, malate, tartrate, fumarate, maleate, mesylate, esilate, benzene sulfonate, tosilate, benzoate, aspartate, glutamate, Glu.As base addition salts, can exemplify inorganic base salts such as sodium salt, calcium salt, magnesium salt, calcium salt, aluminum salt, organic alkali salt and ammonium salts such as ethanolamine salt, lysinate, ornithine salt, meglumine salt, trihydroxy methyl aminomethane salt.
Preferred forms
Chemical compound of the present invention can be prepared according to the step of following (1)～(4).
(1) chemical compound of the present invention (Ia) for example can be prepared according to the method shown in the following reaction equation by amines (V).
[changing 27]
[in the reaction equation, A, R 1, R 2, R 3, R 4, R 5, a is identical with above-mentioned implication with b, Q 1Expression hydroxyl or halogen atoms such as chlorine atom, bromine atoms; Q 2Leaving groups such as expression chlorine atom, bromine atoms, iodine atom, mesyloxy, trifluoro-methanesulfonyl oxy, tolysulfonyl oxygen base, W 1Expression-CO-,-CO-CO-or-SO 2-.]
Step 1: the preparation of amide compound (VII)
(i) use amines (V) and chemical compound (VI) to carry out amidation process, can prepare amide compound (VII).
The Q of chemical compound (VI) 1During for halogen atom, this reaction is preferably reacted in the presence of alkali.As the alkali that uses, can exemplify alkali metal hydroxide (Lithium hydrate, sodium hydroxide, potassium hydroxide etc.), alkali carbonate (lithium carbonate, sodium carbonate, potassium carbonate etc.), alkali metal hydrogencarbonate (sodium bicarbonate, potassium bicarbonate etc.), organic base (triethylamine, diisopropylethylamine, tri-n-butyl amine, 1,5-diazabicylo [4.3.0]-5-nonene, 1,8-diazabicylo [5.4.0]-7-endecatylene, pyridine, N, N-dimethyl aminopyridine etc.) etc.
As reaction temperature, preferred cooling condition is down to the temperature of the boiling point of solvent that uses or reagent, especially preferably-20 ℃～room temperature.
In addition, this reaction can not have solvent or carries out in solvent.As the solvent that uses, can exemplify dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, acetonitrile, ethyl acetate, ethyl methyl ketone, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, water etc.
The solvent that uses in this reaction and the kind of reagent with and consumption preferably suitably select according to employed substrate of reaction and reaction condition.
In addition, the Q of chemical compound (VI) 1During for hydroxyl, the preferred condensing agent that uses, can exemplify phosphorus compound, triphenylphosphine-diethyl azodiformate, N such as sulfonyl chloride compounds such as carbodiimide compound, mesyl chloride, diphenyl phosphatization thing, diphenyl phosphoryl chloride such as alkyl chloroformates such as etherides such as thionyl chloride, oxalyl chloride, ethyl chloroformate, dicyclohexyl carbodiimide, 1-ethyl-3-(3-dimethylamino) propyl carbodiimide diimine as condensing agent, N '-carbonyl dimidazoles etc.
This reaction can not have solvent or carries out in solvent.As the solvent that uses, can exemplify methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, the tert-butyl alcohol, dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, ethyl acetate, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, water etc.
The solvent that uses in this reaction and the kind of reagent and consumption thereof are preferably suitably selected according to employed substrate of reaction and reaction condition.
The (ii) W of chemical compound (VI) 1For-CO-or-during CO-CO-, use the anhydride of chemical compound (VI) or mixed acid anhydride to replace chemical compound (VI), can prepare amide compound (VII).
This reaction is preferably carried out in the presence of alkali, as the alkali that uses, can exemplify alkali metal hydroxide (Lithium hydrate, sodium hydroxide, potassium hydroxide etc.), alkali carbonate (lithium carbonate, sodium carbonate, potassium carbonate etc.), alkali metal hydrogencarbonate (sodium bicarbonate, potassium bicarbonate etc.), organic base (triethylamine, diisopropylethylamine, tri-n-butyl amine, 1,5-diazabicylo [4.3.0]-5-nonene, 1,8-diazabicylo [5.4.0]-7-endecatylene, pyridine, N, N-dimethyl aminopyridine etc.) etc.
As reaction temperature, preferred cooling condition is down to the temperature of the boiling point of solvent that uses or reagent.
In addition, this reaction can not have solvent or carries out in solvent.As the solvent that uses, can exemplify methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, the tert-butyl alcohol, dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, acetonitrile, ethyl acetate, ethyl methyl ketone, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, water etc.
The solvent that uses in this reaction and the kind of reagent and consumption thereof are preferably suitably selected according to employed substrate of reaction and reaction condition.
Step 2: the preparation of The compounds of this invention (Ia)
Make amide compound (VII) and chemical compound (VIII) reaction, can prepare chemical compound of the present invention (Ia).
This reaction is preferably carried out in the presence of alkali, as the alkali that uses, can exemplify alkali metal hydroxide (Lithium hydrate, sodium hydroxide, potassium hydroxide etc.), alkali carbonate (lithium carbonate, sodium carbonate, potassium carbonate etc.), alkali metal hydrogencarbonate (sodium bicarbonate, potassium bicarbonate etc.), alkali metal hydride (sodium hydride, hydrofining etc.), alkali metal (sodium metal, metallic potassium etc.), organic base (triethylamine, diisopropylethylamine, tri-n-butyl amine, 1,5-diazabicylo [4.3.0]-5-nonene, 1,8-diazabicylo [5.4.0]-7-endecatylene, pyridine, N, N-dimethyl aminopyridine etc.), amination alkali metal (Sodamide. etc.), alkali alcoholate (Feldalat NM, Sodium ethylate, potassium tert-butoxide etc.), organo-metallic compound (n-BuLi, s-butyl lithium, tert-butyl lithium, the diisopropylaminoethyl lithium, two (trimethyl silyl) sodium amide etc.) etc.
As reaction temperature, preferred cooling condition is down to the temperature of the boiling point of solvent that uses or reagent.
In addition, this reaction can not have solvent or carries out in solvent.As the solvent that uses, can exemplify methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, the tert-butyl alcohol, dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, ethyl acetate, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride etc.
The solvent that uses in this reaction and the kind of reagent and consumption thereof are preferably suitably selected according to employed substrate of reaction and reaction condition.
(2) W for-CO-NH-or-The compounds of this invention of CS-NH-can use the W of amide compound (VII) 1For-CO-NH-or-chemical compound of CS-NH-, be prepared equally with the preparation method shown in the step 2 of (1).
The W of amide compound (VII) 1For-CO-NH-or-chemical compound of CS-NH-can be by making amines (V) and chemical compound: R 5-NCO or chemical compound: R 5-NCS reaction is prepared.
This reaction can not have solvent or carries out in solvent.
As reaction temperature, preferred cooling condition is down to the temperature of the boiling point of solvent that uses or reagent, as the solvent that uses, can exemplify dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, acetonitrile, ethyl acetate, ethyl methyl ketone, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride etc.
The solvent that uses in this reaction and the kind of reagent and consumption thereof are preferably suitably selected according to employed substrate of reaction and reaction condition.
(3) chemical compound of the present invention (I) can use the group with imine moiety of following formula (IX) expression and chemical compound (VI), chemical compound: R 5-N=C=O or chemical compound: R 5-N=C=S is prepared equally with the step 1 of above-mentioned (1) or the preparation method shown in (2).
[changing 28]
(in the formula, R 1, R 2, R 3, R 4, a is identical with above-mentioned implication with b.)
Group with imine moiety (IX) can be by being prepared The compounds of this invention (I) hydrolysis.
R 5Preferred especially hydrogen atom, C 1-10Alkyl, C 1-6Haloalkyl etc., as hydrolysis, can exemplify separately or combination in any is used the acid hydrolysis of hydrochloric acid, sulphuric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, phosphoric acid, polyphosphoric acid etc., use the basic hydrolysis of Lithium hydrate, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, ammonia etc. etc.
This reaction can not have solvent or carries out in solvent.As the solvent that uses, can exemplify methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, the tert-butyl alcohol, dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, water etc.
As reaction temperature, preferred cooling condition is down to the temperature of the boiling point of solvent that uses or reagent, preferred especially 0 ℃～100 ℃.
In this hydrolysis, the solvent of use and the kind of reagent and consumption thereof are preferably suitably selected according to employed substrate of reaction and reaction condition.
(4) The compounds of this invention of following formula (Ib) expression can be prepared according to following (i) and preparation method (ii).
[changing 29]
Figure A20058003900500841
(in the formula, R 1, R 2, R 3, R 4, R 5, R 13Identical with W with above-mentioned implication.)
(i) chemical compound and the chemical compound of pyrazole compound (X) expression: R 2-Q 3(in the formula, R 2Identical with above-mentioned implication, Q 3Be leaving groups such as chlorine atom, bromine atoms, iodine atom, mesyloxy, trifluoro-methanesulfonyl oxy, tolysulfonyl oxygen base) reacting in the presence of the alkali or under the non-existent condition, can prepare chemical compound of the present invention (Ib).
[changing 30]
(in the formula, R 1, R 4, R 5, R 13Identical with W with above-mentioned implication.)
As the alkali that uses, can exemplify alkali metal hydroxide (Lithium hydrate, sodium hydroxide, potassium hydroxide etc.), alkali carbonate (lithium carbonate, sodium carbonate, potassium carbonate etc.), alkali metal hydrogencarbonate (sodium bicarbonate, potassium bicarbonate etc.), alkali metal hydride (sodium hydride, hydrofining etc.), alkali metal (sodium metal, metallic potassium etc.), organic base (triethylamine, diisopropylethylamine, tri-n-butyl amine, 1,5-diazabicylo [4.3.0]-5-nonene, 1,8-diazabicylo [5.4.0]-7-endecatylene, pyridine, N, N-dimethyl aminopyridine etc.), amination alkali metal (Sodamide. etc.), alkali alcoholate (Feldalat NM, Sodium ethylate, potassium tert-butoxide etc.), organo-metallic compound (n-BuLi, s-butyl lithium, tert-butyl lithium, lithium diisopropylamine, two (trimethyl silyl) Sodamide. etc.) etc.
As reaction temperature, preferred cooling condition is down to the temperature of the boiling point of solvent that uses or reagent.
In addition, this reaction can not have solvent or carries out in solvent.As the solvent that uses, can exemplify dioxane, oxolane, ether, petroleum ether, normal hexane, cyclohexane extraction, benzene,toluene,xylene, chlorobenzene, pyridine, ethyl acetate, N, dinethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride etc.
The solvent that uses in this reaction and the kind of reagent and consumption thereof are preferably suitably selected according to employed substrate of reaction and reaction condition.
The chemical compound that uses in the preparation method shown in (ii) above-mentioned (4) it (i): R 2-Q 3Use chemical compound: (R 2O) 2SO 2(in the formula, R 2Identical with above-mentioned implication.) replace, react equally, can prepare chemical compound of the present invention (Ib).
In addition, when preparing chemical compound of the present invention, according to the kind of functional group, for the intermediate in raw material or the preparation process, protecting this functional group or being transformed into the group that can change into this functional group easily is effective aspect preparation sometimes.As this functional group, can exemplify amino, hydroxyl, carboxyl etc.As its blocking group; can be-as be used for the blocking group of amino, hydroxyl, carboxyl etc., the kind and the consumption thereof of the reaction temperature when protection and deprotection operation, the solvent of use and reagent are preferably suitably selected according to reacting employed substrate and reaction condition.
Chemical compound of the present invention can oral or non-oral administration.Its form of administration is tablet, capsule, granule, powder, powder, lozenge, ointment, cream, Emulsion, suspension, suppository, injection etc., all can make according to habitual preparation technique (for example, the method for the 14th edition Japanese Pharmacopoeia regulation etc.).These form of administration can suitably be selected according to patient's symptom, age and therapeutic purposes.In the manufacturing of the preparation of various dosage forms, (for example can use excipient commonly used, crystalline cellulose, starch, lactose, mannitol etc.), binding agent (for example, hydroxypropyl cellulose, polyvinyl pyrrolidone etc.), lubricant (for example, magnesium stearate, Talcum etc.), disintegrating agent (for example, carboxymethylcellulose calcium etc.) etc.
The dosage of chemical compound of the present invention is 1～2000mg on the 1st when the adult is treated, with its 1 time on the 1st or branch administration for several times.This dosage can suitably increase and decrease according to patient's age, body weight and symptom.
Embodiment
Below in conjunction with embodiment and test example, specify the present invention, but the present invention is not limited to this.
Embodiment 1
1-cyclopropyl methyl-2-(trifluoroacetyl group imino group)-1, the preparation of 2-dihydropyridine (compound N is o.1)
[changing 31]
Figure A20058003900500861
In chloroform (20ml) solution of 2-aminopyridine (2.0g) and pyridine (1.9ml), under ice-cold condition, after the adding trifluoroacetic anhydride (3.3ml), at room temperature stirred 3 days.Washing reaction liquid (pressing the order of water, saturated aqueous common salt), dry (anhydrous sodium sulfate), after the filtration, concentrated filtrate under reduced pressure.(launch solvent: n-hexane-ethyl acetate=3: 1) make with extra care the residue that obtains, obtain 2-(trifluoroacetyl group amino) pyridine (2.3g) of colourless liquid shape with silica gel column chromatography.
2-(trifluoroacetyl group amino) pyridine (1.3g) that obtains is dissolved in N; in the dinethylformamide (13ml); at room temperature add sodium iodide (0.01g), 60% sodium hydride (0.27g) and cyclopropyl methyl bromide (1.1g), 50 ℃ of following heated and stirred 5 hours.Make reactant liquor return to room temperature, add entry, extraction (ethyl acetate), washing (saturated aqueous common salt), dry (anhydrous sodium sulfate), and after the filtration, concentrated filtrate under reduced pressure.(launch solvent: chloroform-methanol=18: 1) make with extra care the residue that obtains, obtain the 1-cyclopropyl methyl-2-(trifluoroacetyl group imino group)-1 of clear crystal shape, 2-dihydropyridine (1.4g) with silica gel column chromatography.
1H-NMR, MS (ESI) and fusing point are as shown in table 8.
Embodiment 2
1-cyclopropyl methyl-2-{3-(trifluoromethyl) benzoyl imino group }-1, the preparation of 2-dihydropyridine (compound N is o.2)
(1) 1-cyclopropyl methyl-2-imino group-1, the 2-dihydropyridine
[changing 32]
Figure A20058003900500871
Will be according to the 1-cyclopropyl methyl-2-(trifluoroacetyl group imino group)-1 of the preparation of the preparation method shown in the embodiment 1; 2-dihydropyridine (1.1g) is dissolved in the methanol (25ml); at room temperature add Anhydrous potassium carbonate (1.2g) is dissolved in the aqueous solution that water (12.5ml) obtains, stirred 2 hours.Extractive reaction liquid (ethyl acetate), dry (anhydrous sodium sulfate), after the filtration, concentrated filtrate under reduced pressure.(launch solvent: chloroform-methanol=18: 1) make with extra care the residue that obtains, obtain the 1-cyclopropyl methyl-2-imino group-1 of yellow liquid shape, 2-dihydropyridine (0.5g) with silica gel column chromatography.
1H-NMR(200MHz，CHLOROFORM-d)d ppm；0.31-0.37(m，2H)，0.58-0.67(m，2H)，1.23-1.43(m，1H)，3.69(d，J＝6.0Hz，2H)，5.70(m，1H)，6.29(d，J＝8.0，1H)，6.76(m，1H)，7.04(m，1H)
MS(ESI)(Positive)m/z；149(M+H) +
(2) 1-cyclopropyl methyl-2-{3-(trifluoromethyl) benzoyl imino group }-1,2-dihydropyridine (compound N is o.2)
[changing 33]
Figure A20058003900500872
At 1-cyclopropyl methyl-2-imino group-1, in chloroform (2ml) solution of 2-dihydropyridine (0.20g) and triethylamine (0.19ml), under ice-cold condition, behind adding 3-(trifluoromethyl) Benzenecarbonyl chloride. (0.24ml), at room temperature stirred 17 hours.In reactant liquor, add entry; extraction (chloroform); dry (anhydrous sodium sulfate); after the filtration; concentrated filtrate under reduced pressure; with silica gel column chromatography (launch solvent: n-hexane-ethyl acetate=3: 1) the refining residue that obtains obtains 1-cyclopropyl methyl-2-{3-(trifluoromethyl) benzoyl imino group of colorless solid shape }-1,2-dihydropyridine (0.44g).
1H-NMR, MS (ESI) and fusing point are as shown in table 8.
Embodiment 3
1-cyclopropyl methyl-2-{3-(trifluoromethyl) phenyl sulfonyl imino group }-1, the preparation of 2-dihydropyridine (compound N is o.50)
[changing 34]
Figure A20058003900500881
According to the preparation method shown in the embodiment 2, replace 3-(trifluoromethyl) Benzenecarbonyl chloride. with 3-(trifluoromethyl) phenyl sulfonic acid chloride, obtain 1-cyclopropyl methyl-2-{3-(trifluoromethyl) phenyl sulfonyl imino group of colorless solid shape }-1, the 2-dihydropyridine.
1H-NMR, Mass and fusing point are as shown in table 8.
Compound N shown in the table 1 o.3-49 with the compound N shown in 51-59, the table 2 o.60, o.504-515 the compound N shown in 71-107,116-174,178-213,215-342,343-351 and 369-372, the table 3 prepare according to the preparation method shown in embodiment 1 and 2.
These chemical compounds 1H-NMR, Mass and fusing point are shown in table 8, table 9 and table 11.
Embodiment 4
The 5-tert-butyl group-3-(2-ethoxyethyl group)-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2, the preparation of 3-thiazoline (compound N is o.352)
(1) the 5-tert-butyl group-4-methyl-2-(3-trifluoromethyl benzoyl) aminothiazole
[changing 35]
With the N of 2-amino-5-tert-butyl group-4-methylthiazol (1.0g), 3-(trifluoromethyl) benzoic acid (1.2g), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimides one hydrochlorate (1.2g) and I-hydroxybenzotriazole monohydrate (1.0g), dinethylformamide (10ml) solution at room temperature stirred 48 hours.In reactant liquor, add ethyl acetate; washing (pressing the order of 2M hydrochloric acid, 2M sodium hydrate aqueous solution, saturated aqueous common salt); dry (anhydrous sodium sulfate); after the filtration; concentrated filtrate under reduced pressure obtains the yellow unbodied 5-tert-butyl group-4-methyl-2-(3-trifluoromethyl benzoyl) aminothiazole (1.7g).
1H-NMR(200MHz，CHLOROFORM-D)d ppm；1.42(s，9H)，2.20(s，3H)，7.55(t，J＝7.5Hz，1H)，7.78(d，J＝7.5Hz，1H)，8.05(d，J＝7.5Hz，1H)，8.16(s，1H)
MS(ESI)(Positive)m/z；343(M+H)
(2) the 5-tert-butyl group-3-(2-ethoxyethyl group)-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2,3-thiazoline (compound N is o.352)
[changing 36]
Figure A20058003900500892
The N that will contain the 5-tert-butyl group-4-methyl-2-(3-trifluoromethyl benzoyl) aminothiazole (0.15g), sodium iodide (0.005g), 60% sodium hydride (0.02g) and 2-ethoxy ethyl bromide (0.11g), dinethylformamide (1.5ml) solution was 50 ℃ of following heated and stirred 5 hours.Make reactant liquor return to room temperature, add entry, extraction (ethyl acetate), washing (saturated aqueous common salt), dry (anhydrous sodium sulfate), and after the filtration, concentrated filtrate under reduced pressure.(launch solvent: n-hexane-ethyl acetate=5: 1) make with extra care the residue that obtains with silica gel column chromatography; obtain the 5-tert-butyl group-3-(2-ethoxyethyl group)-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2 of clear crystal shape, 3-thiazoline (0.03g).
1H-NMR, Mass and fusing point are as shown in table 9.
Compound N shown in the table 2 o.384-430,433,434 and 438-447 prepare according to the preparation method shown in the embodiment 3.
These chemical compounds 1H-NMR, Mass and fusing point are as shown in table 10.
Embodiment 5
The preparation of N-(the 5-tert-butyl group-3-cyclopropyl methyl-4-methyl-3H-thiazole-2-ylides)-1-naphthalene sulfonylamide (compound N o.383)
(1) N-(the 5-tert-butyl group-4-methylthiazol-2-yl)-1-naphthalene sulfonylamide
[changing 37]
Figure A20058003900500901
At 2-amino-5-tert-butyl group-4-methylthiazol (0.12g) and N, in pyridine (1.5ml) solution of N-dimethyl aminopyridine (catalytic amount), under ice-cold condition, add 1-naphthalene sulfonyl chloride (0.19g), at room temperature stir and spend the night.In reactant liquor, add entry, filter and collect precipitate, drying.With the coarse crystal recrystallization (chloroform-n-hexane) that obtains, obtain N-(the 5-tert-butyl group-4-methylthiazol-2-yl)-1-naphthalene sulfonylamide (0.22g) of clear crystal shape.
1H-NMR(200MHz，CHLOROFORM-D)d ppm；1.43(s，9H)，2.36(s，3H)
MS(ESI)(Negative)m/z；265(M-H) -
(2) N-(the 5-tert-butyl group-3-cyclopropyl methyl-4-methyl-3H-thiazole-2-ylides)-1-naphthalene sulfonylamide (compound N o.383)
[changing 38]
Figure A20058003900500911
With the N of N-(the 5-tert-butyl group-4-methyl-thiazol-2-yl)-1-naphthalene sulfonylamide (0.20g), 55% sodium hydride (0.03g), sodium iodide (catalytic amount) and (bromomethyl) cyclopropane (0.11g), dinethylformamide (0.5ml) solution at room temperature stirs and spends the night.In reactant liquor, add entry, extraction (ethyl acetate), washing (pressing the order of water, saturated aqueous common salt), dry (anhydrous magnesium sulfate), and after the filtration, concentrated filtrate under reduced pressure.(launch solvent: n-hexane-ethyl acetate=4: 1) make with extra care the residue that obtains with silica gel column chromatography, recrystallization (chloroform-n-hexane) obtains N-(the 5-tert-butyl group-3-cyclopropyl methyl-4-methyl-3H-thiazole-2-ylides)-1-naphthalene sulfonylamide (0.12g) of clear crystal shape.
1H-NMR, Mass and fusing point are as shown in table 10.
Embodiment 6
3-(2-the amino-ethyl)-5-tert-butyl group-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2, the preparation of 3-thiazoline (compound N is o.354)
[changing 39]
Figure A20058003900500912
To contain 3-(2-the phthaloyl sub-aminoethyl)-5-tert-butyl group-4-methyl-2-(the 3-trifluoromethyl benzoyl) imino group-2 according to the preparation of the preparation method of embodiment 4,3-thiazoline (compound N o.355) (0.15g) and ethanol (6.3ml) vlil of hydrazine monohydrate (0.2ml) 1 hour.Make reactant liquor return to room temperature, remove by filter precipitate.In filtrate, add chloroform; washing (pressing the order of 2M sodium hydrate aqueous solution, saturated aqueous common salt); dry (anhydrous magnesium sulfate); after the filtration; concentrated filtrate under reduced pressure; obtain 3-(2-the amino-ethyl)-5-tert-butyl group-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2 of light yellow crystal shape, 3-thiazoline (0.12g).
1H-NMR, Mass and fusing point are as shown in table 9.
Embodiment 7
5-carboxyl-3-cyclopropyl methyl-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2, the preparation of 3-thiazoline (compound N is o.357)
[changing 40]
Figure A20058003900500921
To contain 5-ethoxy carbonyl-3-cyclopropyl methyl-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2 according to the preparation method shown in the embodiment 4 preparation, 3-thiazoline (compound N o.356) (0.23g) and 1: 1 tetrahydrofuran-ethyl alcohol (8ml) solution of 20% sodium hydrate aqueous solution (1.25ml) at room temperature stirred 1 hour.In reactant liquor, add 3M hydrochloric acid, be adjusted to acidity after, filter and collect precipitate.The solid that obtains is dissolved in oxolane-chloroform; dry (anhydrous magnesium sulfate), after the filtration, concentrated filtrate under reduced pressure; obtain colourless unbodied 5-carboxyl-3-cyclopropyl methyl-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2,3-thiazoline (0.20g).
1H-NMR, Mass and fusing point are as shown in table 9.
Compound N shown in the table 2 o.214, o.431 the compound N shown in the table 3 prepare according to the preparation method shown in the embodiment 7 with 435.
These chemical compounds 1H-NMR, Mass and fusing point are shown in table 9, table 10 and table 11.
Embodiment 8
3-cyclopropyl methyl-5-isopropyl amino carbonyl 4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2, the preparation of 3-thiazoline (compound N is o.358)
[changing 41]
Figure A20058003900500931
Use is according to 5-carboxyl-3-cyclopropyl methyl-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2 of the preparation of the preparation method shown in the embodiment 7; 3-thiazoline (compound N o.357); according to the preparation method shown in the embodiment 3 (1); obtain 3-cyclopropyl methyl-5-isopropyl amino carbonyl-4-methyl-2-(3-trifluoromethyl benzoyl) imino group-2 of colourless powder shape, the 3-thiazoline.
1H-NMR, Mass and fusing point are as shown in table 9.
According to the preparation example shown in the embodiment 8, use compound N o.356, the preparation compound N is o.359-361.
Use compound N o.431 to prepare compound N equally o.432.
Use compound N o.435 to prepare compound N equally o.436 with 437.
These chemical compounds 1H-NMR, Mass and fusing point are shown in table 9 and table 10.
Embodiment 9
The preparation of N-(3-pi-allyl-4,5-diphenyl-3H-thiazole-2-ylides) Benzoylamide (compound N o.368)
(1) 1-pi-allyl-3-benzoylthioureas
[changing 42]
Figure A20058003900500932
Benzene (9ml) solution of benzoyl isothiocyanate (1.4g) and allylamine (0.7ml) at room temperature stirred spend the night.Under reduced pressure, behind the concentration of reaction solution, (launch solvent: n-hexane-ethyl acetate=10: 1～5: 1) make with extra care the residue that obtains, obtain the 1-pi-allyl-3-benzoylthioureas (1.9g) of colorless solid shape with silica gel column chromatography.
1H-NMR(200MHz，CHLOROFORM-D)d ppm；4.30-4.43(m，2H)，5.21-5.42(m，2H)，5.87-6.09(m，1H)，7.45-7.69(m，3H)，7.78-7.90(m，2H)，9.00(s，1H)，10.80(s，1H)，
MS(ESI)(Negative)m/z；219(M-H) -
Fusing point 68-69 ℃
(2) N-(3-pi-allyl-4,5-diphenyl-3H-thiazole-2-ylides) Benzoylamide (compound N o.368)
[changing 43]
Figure A20058003900500941
With 1-pi-allyl-3-benzoylthioureas (0.20g) and 2-bromo-1, toluene (4.5ml) vlil of 2-diphenylethane (0.24g) 4.5 hours.Under reduced pressure behind the concentrated solvent, (launch solvent: n-hexane-ethyl acetate=30: 1～20: 1) make with extra care the residue that obtains with silica gel column chromatography, carry out recrystallization (n-hexane-ethyl acetate), obtain N-(3-pi-allyl-4, the 5-diphenyl-3H-thiazole-2-ylides) Benzoylamide (0.13g) of clear crystal shape.
1H-NMR, Mass and fusing point are as shown in table 9.
Embodiment 10
N-[1,2-dihydro-1,5-dimethyl-2-(2-ethoxyethyl group) pyrazoles-3-subunit]-preparation of 2-fluoro-3-(trifluoromethyl) Benzoylamide (compound N is o.452)
(1) N-(1,5-dimethyl pyrazole-3-yl)-2-fluoro-3-(trifluoromethyl) Benzoylamide
[changing 44]
Figure A20058003900500951
At 3-amino-1, in chloroform (5ml) solution of 5-dimethyl pyrazole (0.50g) and triethylamine (0.63ml), under ice-cold condition, behind adding 2-fluoro-3-(trifluoromethyl) Benzenecarbonyl chloride. (0.65ml), at room temperature stirred 0.5 hour.Washing reaction liquid (2M sodium hydrate aqueous solution), dry (anhydrous sodium sulfate) is after the filtration, concentrated filtrate under reduced pressure, with the residue that the normal hexane washing obtains, obtain N-(1,5-dimethyl pyrazole-3-yl)-2-fluoro-3-(trifluoromethyl) Benzoylamide (1.25g) of colorless solid shape.
1H-NMR(200MHz，CHLOROFORM-D)d ppm；2.30(s，39H)，3.72(s，3H)，6.59(s，1H)，7.40(t，J＝7.5Hz，1H)，7.78(t，J＝7.5Hz，1H)，8.34(td，J＝7.5Hz，1H)，8.60-8.89.(br.s，1H)
MS(ESI)(Positive)m/z；302(M+H) +
(2) N-[1,2-dihydro-1,5-dimethyl-2-(2-ethoxyethyl group) pyrazoles-3-subunit]-2-fluoro-3-(trifluoromethyl) Benzoylamide
[changing 45]
Figure A20058003900500952
With N-(1,5-dimethyl pyrazole-3-yl)-N of 2-fluoro-3-(trifluoromethyl) Benzoylamide (0.50g) and 55% sodium hydride (0.07g), after dinethylformamide (5ml) suspension at room temperature stirs 5 minutes, add 2-ethoxy ethyl bromide (0.38g) and sodium iodide (catalytic amount), stirred 17 hours.In reactant liquor, add entry, behind ethyl acetate extraction, under reduced pressure, concentrate.(launch solvent: chloroform-methanol=18: 1) make with extra care the residue that obtains with silica gel column chromatography, obtain the N-[1 of colorless solid shape, 2-dihydro-1,5-dimethyl-2-(2-ethoxyethyl group) pyrazoles-3-subunit]-2-fluoro-3-(trifluoromethyl) Benzoylamide (0.01g).
1H-NMR, Mass and fusing point are as shown in table 11.
Compound N shown in the table 3 o.448-451,453,454 and 456 prepare according to the preparation method shown in the embodiment 10.
These chemical compounds 1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 11
N-{1,2-dihydro-1,5-dimethyl-2-(1,1-dioxo Tetramethylene sulfide-3-yl) pyrazoles-3-subunit }-preparation of 2-fluoro-3-(trifluoromethyl) Benzoylamide (compound N is o.455)
(1) N-{2-(1,1-dioxo Tetramethylene sulfide-3-yl)-5-methylpyrazole-3-yl }-2-fluoro-3-(trifluoromethyl) Benzoylamide
[changing 46]
Figure A20058003900500961
Use 3-amino-2-(1,1-dioxo Tetramethylene sulfide-3-yl)-the 5-methylpyrazole, according to the preparation method shown in the embodiment 8 (1), obtain N-{2-(1,1-dioxo Tetramethylene sulfide-3-the yl)-5-methylpyrazole-3-yl of colorless solid shape)-2-fluoro-3-(trifluoromethyl) Benzoylamide.
1H-NMR(600MHz，CHLOROFORM-D)d ppm；2.63-2.69(m，1H)，2.75-2.81(m，1H)，3.12(m，1H)，3.50-3.63(m，3H)，4.89(m，1H)，6.00(s，1H)，7.46(m，1H)，7.87(m，1H)，8.13(d，J＝13.3Hz，1H)，8.33(m，1H)
MS(ESI)(Positive)m/z；406(M+H) +
(2) N-{1,2-dihydro-1,5-dimethyl-2-(1,1-dioxo Tetramethylene sulfide-3-yl) pyrazoles-3-subunit }-2-fluoro-3-(trifluoromethyl) Benzoylamide (compound N is o.455)
[changing 47]
Figure A20058003900500971
With N-{2-(1,1-dioxo Tetramethylene sulfide-3-yl)-5-methylpyrazole-3-yl }-toluene (1.2ml) solution of 2-fluoro-3-(trifluoromethyl) Benzoylamide (0.40g) and dimethyl sulfate (0.11ml) is 80 ℃ of following heated and stirred 47 hours.Make reactant liquor return to room temperature, (launch solvent: chloroform-methanol=20: 1) make with extra care with silica gel column chromatography, obtain colourless unbodied N-{1,2-dihydro-1,5-dimethyl-2-(1,1-dioxo Tetramethylene sulfide-3-yl) pyrazoles-3-subunit }-2-fluoro-3-(trifluoromethyl) Benzoylamide (0.11g).
1H-NMR, Mass and fusing point are as shown in table 11.
Compound N shown in the table 3 chemical compound o.497-499 prepares according to the preparation method shown in the embodiment 11.
1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 12
The preparation of N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit) Methanamide (compound N o.457)
(1) the 3-amino-5-tert-butyl group-2-(cyclopropyl methyl) pyrazoles
[changing 48]
Figure A20058003900500972
In chloroform (500ml) solution of cyclopropyl-carbinol (125g) and triethylamine (315ml), under ice-cold condition, added mesyl chloride (175ml) with 1.5 hours after, at room temperature stirred 2 hours.In reactant liquor, add entry, extraction (chloroform), washing (pressing the order of water, saturated aqueous common salt), dry (anhydrous magnesium sulfate), and after the filtration, concentrated filtrate under reduced pressure.The residue (232g) that obtains is dissolved in the ethanol (500ml), at room temperature, adds hydrazine 1 hydrate (500g), stirred 17 hours.After distillation removes and desolvates under reduced pressure, extraction (chloroform), dry (anhydrous magnesium sulfate) filters concentrated filtrate under reduced pressure.The yellow oily residue (68g) that obtains is dissolved in the ethanol (610ml), at room temperature, adds 4, behind 4-dimethyl-3-oxo valeronitrile (99g), refluxed 4 hours.After distillation removes and desolvates under reduced pressure, (launch solvent: n-hexane-ethyl acetate=5: 1) make with extra care with silica gel column chromatography, recrystallization (ethyl acetate-n-hexane) obtains the 3-amino-5-tert-butyl group-2-(cyclopropyl methyl) pyrazoles (80g) of colorless solid shape.
1H-NMR(200MHz，CHLOROFORM-d)d ppm；0.26-0.41(m，2H)，0.49-0.62(m，2H)，1.11-1.27(m，1H)，1.26(s，9H)3.42(br.s，2H)，3.86(d，J＝6.2Hz，2H)，5.42(s，1H)
MS(ESI)(Positive)m/z；194(M+H) +
Fusing point 69.5-70.5 ℃
(2) N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide
[changing 49]
Figure A20058003900500981
After formic acid (3.9ml) and acetic anhydride (7.4ml) at room temperature stirred 1 hour, under ice-cold condition, add the 3-amino-5-tert-butyl group-2-(cyclopropyl methyl) pyrazoles (5.0g), at room temperature stirred 1 hour.In reactant liquor, add the 2M sodium hydrate aqueous solution, extraction (sodium acetate), washing (water), dry (anhydrous sodium sulfate), after the filtration, concentrated filtrate under reduced pressure obtains N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) Methanamide (4.4g) of colorless oil.
1H-NMR(200MHz，CHLOROFORM-d)d ppm；0.27-0.40(m，2H)，0.50-0.66(m，2H)，1.13-1.27(m，1H)，1.29(s，9H)，3.91(d，J＝6.6Hz，2H)，5.98(s，3H)，6.26(s，3H)，8.26-8.31(m，3H)，8.31-8.39(m，3H)
MS(ESI)(Positive)m/z；222(M+H) +
(3) N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit) Methanamide (compound N o.457)
[changing 50]
Figure A20058003900500991
In toluene (6ml) solution of N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) Methanamide (2.0g), add dimethyl sulfate (0.9ml), 50 ℃ of following heated and stirred 48 hours.Make reactant liquor return to room temperature, add saturated sodium bicarbonate aqueous solution, extraction (ethyl acetate), washing (pressing the order of water, saturated aqueous common salt), dry (anhydrous magnesium sulfate), and after the filtration, concentrated filtrate under reduced pressure.(launch solvent: chloroform-methanol=18: 1) make with extra care the residue that obtains, obtain N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, the 2-dihydro-1-methylpyrazole-3-subunit) Methanamide (0.35g) of colorless solid shape with silica gel column chromatography.
1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 13
The preparation of N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide (compound N o.458)
(1) N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide
[changing 51]
Figure A20058003900501001
Use is according to the 3-amino-5-tert-butyl group-2-(cyclopropyl methyl) pyrazoles of the preparation of the preparation method shown in the embodiment 12 (1), be prepared according to the preparation method shown in the embodiment 1, obtain N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide.
1H-NMR(200MHz，CHLOROFORM-d)d ppm；0.32-0.42(m，2H)，0.65-0.74(m，2H)，1.10-1.36(m，1H)，1.30(s，9H)，3.99(d，J＝6.0Hz，2H)，6.31(s，1H)，8.11-8.23(brs，1H)
MS(ESI)(Negative)m/z；290(M+H) +
(2) N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide (compound N o.458)
[changing 52]
Figure A20058003900501002
According to the preparation method shown in the embodiment 12 (3), obtain N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide by N-(the 5-tert-butyl group-2-cyclopropyl methylpyrazole-3-yl) trifluoroacetamide.
1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 14
The preparation of N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-2-chloro-3-(trifluoromethyl) Benzoylamide (compound N o.476)
(1) the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-ylidene amines
[changing 53]
Figure A20058003900501011
To at room temperature stir 2 hours according to N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, the 2-dihydro-1-methylpyrazole-3-subunit) Methanamide (0.20g) of the preparation of the preparation method shown in the embodiment 12 and methanol (3ml) solution of 12M hydrochloric acid (0.3ml).In reactant liquor, add the 2M sodium hydrate aqueous solution, after being adjusted to alkalescence, extraction (chloroform), dry (anhydrous sodium sulfate), filter, concentrated filtrate under reduced pressure obtains the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid of yellow amorphous solid shape, 2-dihydro-1-methylpyrazole-3-ylidene amines (0.17g).
1H-NMR(200MHz，CHLOROFORM-d)d ppm；0.28-0.41(m，2H)，0.43-0.55(m，2H)，0.95-1.17(m，1H)，1.29(s，9H)，3.16(s，3H)，3.62(d，J＝6.6Hz，2H)，5.31(s，1H)
MS(ESI)(Negative)m/z；208(M+H) +
(2) N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-2-chloro-3-(trifluoromethyl) Benzoylamide (compound N o.476)
[changing 54]
Figure A20058003900501012
With 2-chloro-3-trifluoromethyl benzoic acid (0.13g), thionyl chloride (0.07ml) and N, oxolane (2ml) vlil of dinethylformamide (0.01ml) 0.5 hour.After distillation removes and desolvates under reduced pressure, in the residue that obtains, add chloroform (1ml), obtain chloroformic solution.This chloroformic solution is at room temperature joined the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid-methyl isophthalic acid, in chloroform (2ml) solution of 2-pyrazoline-3-ylidene amines (0.10g) and triethylamine (0.10ml), stirred 17 hours.Washing reaction liquid (pressing the order of saturated sodium bicarbonate aqueous solution, saturated sodium-chloride water solution), dry (anhydrous magnesium sulfate), after the filtration, concentrated filtrate under reduced pressure.(launch solvent: ethyl acetate-methanol=5: 1) make with extra care the residue that obtains with silica gel column chromatography, obtain N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-2-chloro-3-(trifluoromethyl) Benzoylamide (0.05g) of colorless solid shape.
1H-NMR, Mass and fusing point are as shown in table 11.
Compound N shown in the table 3 o.459-473,475,477-496 and 503 prepares according to the preparation method shown in the embodiment 14.
These chemical compounds 1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 15
The preparation of N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-2-fluoro-3-(trifluoromethyl) Benzoylamide (compound N o.474)
[changing 55]
In chloroform (120ml) solution of the 3-amino-5-tert-butyl group-2-(cyclopropyl methyl) pyrazoles (12.8g) and triethylamine (9.2ml), under ice-cold condition, behind adding 2-fluoro-3-(trifluoromethyl) Benzenecarbonyl chloride. (15.0g), at room temperature stirred 1 hour.Washing reaction liquid (2M sodium hydrate aqueous solution), dry (anhydrous sodium sulfate), after the filtration, concentrated filtrate under reduced pressure.(launch solvent: n-hexane-ethyl acetate=3: 1) make with extra care the residue that obtains, obtain colorless solid (18.3g) with silica gel column chromatography.The solid (4.4g) that obtains with toluene (90ml) dissolving, is added dimethyl sulfate (3.2ml), 80 ℃ of following heated and stirred 17 hours.Make reactant liquor return to room temperature, add saturated sodium bicarbonate aqueous solution, extraction (ethyl acetate), washing (pressing the order of water, saturated aqueous common salt), dry (anhydrous sodium sulfate), and after the filtration, concentrated filtrate under reduced pressure.(launch solvent: chloroform-methanol=18: 1) make with extra care the residue that obtains with silica gel column chromatography, obtain N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-2-fluoro-3-(trifluoromethyl) Benzoylamide (0.3g) of colorless solid shape.
1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 16
The preparation of N-(the 5-tert-butyl group-2-cyclobutylmethyl-1,2-dihydro-1-methylpyrazole-3-subunit)-2-fluoro-3-(trifluoromethyl) Benzoylamide (compound N o.482)
[changing 56]
Figure A20058003900501031
Use is according to the 3-amino-5-tert-butyl group-2-(cyclobutylmethyl) pyrazoles of the preparation of the preparation method shown in the embodiment 12 (1), be prepared according to the preparation method shown in the embodiment 15, obtain N-(the 5-tert-butyl group-2-cyclobutylmethyl-1,2-dihydro-1-methylpyrazole-3-subunit)-2-fluoro-3-(trifluoromethyl) Benzoylamide.
1H-NMR, Mass and fusing point are as shown in table 11.
O.481, compound N shown in the table 3 prepares according to the preparation method shown in the embodiment 16 with 483-496.
These chemical compounds 1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 17
N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-3, the preparation of 5-difluorophenyl oxo acetamide (compound N is o.500)
[changing 57]
Figure A20058003900501041
Will be according to the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid of the preparation of the preparation method shown in the embodiment 14 (1), 2-dihydro-1-methylpyrazole-3-ylidene amines (0.080g) and 3, the mixture of 5-difluorophenyl oxo ethyl acetate (0.2ml) was 110 ℃ of following heated and stirred 7 hours.Make mixture return to room temperature, with silica gel column chromatography (expansion solvent: chloroform-methanol=30: 1), then (launch solvent: n-hexane-ethyl acetate=1: 10) carry out separation and purification with thin layer chromatography, obtain filbert unbodied N-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-3,5-difluorophenyl oxo acetamide (0.5mg).
1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 18
1-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-3-{4-chloro-2-(trifluoromethyl) phenyl } preparation of urea (compound N is o.501)
[changing 58]
Figure A20058003900501042
To contain the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid according to the preparation of the preparation method shown in the embodiment 14 (1), oxolane (2ml) solution of 2-dihydro-1-methylpyrazole-3-ylidene amines (0.050g) and 4-chloro-2-(trifluoromethyl) phenyl isocyanate (0.064g) at room temperature stirred 20 hours.In reactant liquor, add entry, extraction (ethyl acetate), washing (pressing the order of water, saturated aqueous common salt), dry (anhydrous magnesium sulfate), and after the filtration, concentrated filtrate under reduced pressure.(launch solvent: the residue that obtains of separation and purification chloroform-methanol=25: 1) with thin layer chromatography, obtain 1-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-3-{4-chloro-2-(trifluoromethyl) phenyl of pale yellow powder shape } urea (0.001g).
1H-NMR, Mass and fusing point are as shown in table 11.
Embodiment 19
The preparation of 1-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-3-(4-fluorophenyl) thiourea (compound N o.502)
[changing 59]
According to the preparation method shown in the embodiment 18, obtain 1-(the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-subunit)-3-(4-fluorophenyl) thiourea.
1H-NMR, Mass and fusing point are as shown in table 11.
Compound N shown in table 4～table 7 o.1001～1431,2001～2678,3001～3158 and 3159～3327 chemical compound is according to the preparation method shown in embodiment 2 (2) or the embodiment 14 (2), use group with imine moiety (1-cyclopropyl methyl-2-imino group-1, the 2-dihydropyridine, 3-cyclopropyl methyl-2,3-dihydro-4,5-dimethylthiazole-2-ylidene amines, the 5-tert-butyl group-2,3-dihydro-3,4-dimethylthiazole-2-ylidene amines, the 5-tert-butyl group-2,3-dihydro-3-ethyl-4-methylthiazol-2-ylidene amines, the 5-tert-butyl group-2,3-dihydro-3-(2-methoxy ethyl)-4-methylthiazol-2-ylidene amines, the 5-tert-butyl group-3-cyclopropyl methyl-2,3-dihydro-4-methylthiazol-2-ylidene amines, the 5-tert-butyl group-2-cyclopropyl methyl isophthalic acid, 2-dihydro-1-methylpyrazole-3-the ylidene amines and the 5-tert-butyl group-3-cyclopropyl methyl-2,3-dihydro-1,3,4-thiadiazoles-2-ylidene amines) preparation.
The Mass of the chemical compound that obtains is shown in table 12～15.
Table 1
Figure A20058003900501061
Table 1 (continuing)
Figure A20058003900501071
Table 1 (continuing)
Table 1 (continuing)
Figure A20058003900501091
Table 1 (continuing)
Figure A20058003900501101
Table 1 (continuing)
Figure A20058003900501111
Table 2
Table 2 (continuing)
Figure A20058003900501131
Table 2 (continuing)
Table 2 (continuing)
Table 2 (continuing)
Figure A20058003900501161
Table 2 (continuing)
Table 2 (continuing)
Table 2 (continuing)
Table 2 (continuing)
Figure A20058003900501201
Table 2 (continuing)
Table 2 (continuing)
Figure A20058003900501221
Table 2 (continuing)
Figure A20058003900501231
Table 2 (continuing)
Figure A20058003900501241
Table 2 (continuing)
Table 2 (continuing)
Figure A20058003900501261
Table 2 (continuing)
Figure A20058003900501271
Table 2 (continuing)
Figure A20058003900501281
Table 2 (continuing)
Figure A20058003900501291
Table 2 (continuing)
Figure A20058003900501301
Table 2 (continuing)
Figure A20058003900501311
Table 2 (continuing)
Figure A20058003900501321
Table 2 (continuing)
Figure A20058003900501331
Table 2 (continuing)
Figure A20058003900501341
Table 2 (continuing)
Figure A20058003900501351
Table 2 (continuing)
Table 2 (continuing)
Table 2 (continuing)
Figure A20058003900501381
Table 2 (continuing)
Table 2 (continuing)
Figure A20058003900501401
Table 2 (continuing)
Figure A20058003900501411
Table 2 (continuing)
Figure A20058003900501421
Table 2 (continuing)
Figure A20058003900501431
Table 2 (continuing)
Figure A20058003900501441
Table 3
Figure A20058003900501451
Table 3 (continuing)
Table 3 (continuing)
Figure A20058003900501471
Table 3 (continuing)
Figure A20058003900501481
Table 3 (continuing)
Figure A20058003900501491
Table 3 (continuing)
Figure A20058003900501501
Table 3 (continuing)
Figure A20058003900501511
Table 4
Figure A20058003900501521
Figure A20058003900501522
Table 4 (continuing)
Figure A20058003900501531
Table 4 (continuing)
Figure A20058003900501541
Table 4 (continuing)
Figure A20058003900501551
Table 4 (continuing)
Figure A20058003900501561
Table 4 (continuing)
Figure A20058003900501571
Table 4 (continuing)
Figure A20058003900501581
Table 4 (continuing)
Table 4 (continuing)
Figure A20058003900501601
Table 4 (continuing)
Figure A20058003900501611
Table 4 (continuing)
Figure A20058003900501621
Table 4 (continuing)
Table 4 (continuing)
Figure A20058003900501641
Table 4 (continuing)
Figure A20058003900501651
Table 4 (continuing)
Figure A20058003900501661
Table 4 (continuing)
Table 4 (continuing)
Table 4 (continuing)
Table 4 (continuing)
Figure A20058003900501701
Table 4 (continuing)
Figure A20058003900501711
Table 4 (continuing)
Figure A20058003900501721
Table 4 (continuing)
Figure A20058003900501731
Table 4 (continuing)
Figure A20058003900501741
Table 4 (continuing)
Figure A20058003900501751
Table 4 (continuing)
Figure A20058003900501761
Table 4 (continuing)
Figure A20058003900501771
Table 4 (continuing)
Figure A20058003900501781
Table 5-1)
Figure A20058003900501791
Table 5-1) (continuing)
Figure A20058003900501801
Table 5-1) (continuing)
Figure A20058003900501811
Table 5-2)
Figure A20058003900501821
Table 5-2) (continuing)
Figure A20058003900501831
Table 5-2) (continuing)
Figure A20058003900501841
Table 5-2) (continuing)
Figure A20058003900501851
Table 5-3)
Figure A20058003900501861
Figure A20058003900501862
Table 5-3) (continuing)
Figure A20058003900501871
Table 5-3) (continuing)
Figure A20058003900501881
Table 5-3) (continuing)
Figure A20058003900501891
Table 5-4).
Figure A20058003900501902
Table 5-4). (continuing)
Figure A20058003900501911
Table 5-4). (continuing)
Figure A20058003900501921
Table 5-4). (continuing)
Figure A20058003900501931
Table 5-4). (continuing)
Figure A20058003900501941
Table 5-5)
Figure A20058003900501951
Figure A20058003900501952
Table 5-5) (continuing)
Table 5-5) (continuing)
Figure A20058003900501971
Table 5-5) (continuing)
Figure A20058003900501981
Table 5-5) (continuing)
Figure A20058003900501991
Table 5-5) (continuing)
Figure A20058003900502001
Table 5-5) (continuing)
Table 5-5) (continuing)
Figure A20058003900502021
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Figure A20058003900502031
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Figure A20058003900502041
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Figure A20058003900502051
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Figure A20058003900502061
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Figure A20058003900502071
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Figure A20058003900502081
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Figure A20058003900502091
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Figure A20058003900502111
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Figure A20058003900502121
Table 5-5) (continuing)
Table 6
Figure A20058003900502141
Figure A20058003900502142
Table 6 (continuing)
Table 6 (continuing)
Figure A20058003900502161
Table 6 (continuing)
Figure A20058003900502171
Table 6 (continuing)
Figure A20058003900502181
Table 6 (continuing)
Figure A20058003900502191
Table 6 (continuing)
Figure A20058003900502201
Table 6 (continuing)
Figure A20058003900502211
Table 6 (continuing)
Figure A20058003900502221
Table 6 (continuing)
Table 7
Figure A20058003900502241
Figure A20058003900502242
Table 7 (continuing)
Table 7 (continuing)
Figure A20058003900502261
Table 7 (continuing)
Figure A20058003900502271
Table 7 (continuing)
Figure A20058003900502281
Table 7 (continuing)
Figure A20058003900502291
Table 7 (continuing)
Figure A20058003900502301
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Figure A20058003900502311
Table 7 (continuing)
Figure A20058003900502321
Table 7 (continuing)
Table 7 (continuing)
Figure A20058003900502341
Table 8
Compound N o. 1H-NMR Mass Fusing point (℃)
1 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.53(m，2H)0.61-0.71(m， 2H)1.30-1.47(m，1H)4.25(d，J＝7.31H，2H)6.82-6.92(m，1H)7.73-7.895 (m，2H)8.44-8.51(m，1H) ESI(Pos)245 (M+H) + 90-91
2 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.55(m，2H)0.62-0.78(m， 2H)1.40-1.60(m，1H)4.24(d，J＝7.47Hz，2H)6.56-6.69(m，1H)7.45-7.75 (m，4H)8.38-8.59(m，3H) ESI(Pos)321 (M+H) + 105.5-106.5
3 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.76(m，4H)1.39-1.56(m， 1H)4.22(d，J＝7.0Hz，2H)6.53-6.65(m，1H)7.06-7.22(m，1H)7.52-7.81 (m，3H)8.17-8.27(m，1H)8.32-8.43(m，1H)8.58-8.65(m，1H) ESI(Pos)379 (M+H) + -
4 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.53-0.73(m，2H)1.23-1.53(m， 1H)4.14(d，J＝7.47Hz，2H)6.53-6.68(m，1H)7.20-7.46(m，3H)7.49-7.64 (m，1H)7.64-7.77(m，1H)7.85-8.03(m，1H)8.22-8.37(m，1H) ESI(Pos)337 (M+H) + -
5 1H NMR(200MHz，CHLOROFORM-d)d ppm 3.90(s，3H)6.56-6.70(m，1H) 7.18-7.31(m，1H)7.58-7.71(m，3H)8.17-8.29(m，1H)8.37-8.48(m，1H) ESI(Pos)299 (M+H) + 146-147
6 1H NMR(200MHz，CHLOROFORM-d)d ppm 1.49(t，J＝7.3Hz，3H)4.40(q，J＝7.3 Hz，2H)6.60-6.71(m，1H)7.18-7.31(m，1H)7.56-7.69(m，3H)8.16-8.27 (m，1H)8.39-8.48(m，1H) ESI(Pos)313 (M+H) + 93-95
7 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.97(t，J＝7.3Hz，3H)1.41(dt， J＝14.8，7.3Hz，2H)1.77-1.97(m，2H)4.34(t，J＝7.5Hz，2H)6.55-6.70(m，1 H)7.17-7.31(m，1H)7.55-7.70(m，3H)8.15-8.28(m，1H)8.41-8.50(m，1 H) ESI(Pos)341 (M+H) + 51-52
8 1H NMR(200MHz，CHLOROFORM-d)d ppm 1.47(d，J＝6.6Hz，6H)5.84-6.06 (m，1H)6.64-6.77(m，1H)7.18-7.32(m，1H)7.53-7.78(m，2H)8.14-8.45 (m，2H) ESI(Pos)327 (M+H) + 86-88
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
9 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.74(m，4H)1.32-1.53(m， 1H)4.22(d，J＝7.03Hz，2H)6.61-6.72(m，1H)7.18-7.31(m，1H)7.54-7.76 (m，3H)8.13-8.27(m，1H)8.37-8.48(m，1H) ESI(Pos)339 (M+H) + 58.5-59
10 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.36-0.51(m，2H)0.60-0.74(m， 2H)1.29-1.53(m，1H)4.17(d，J＝7.47Hz，2H)6.58-6.74(m，1H)7.16-7.41 (m，2H)7.55-7.82(m，3H)8.33-8.45(m，1H) ESI(Pos)322 (M+H) + 53.5-54.5
11 1H NMR(300MHz，CHLOROFORM-d)d ppm 0.35-0.75(m，4H)1.18-1.42(m， 1H)4.12(d，J＝7.31Hz，2H)6.61-6.71(m，1H)7.19-7.42(m，2H)7.58-7.85 (m，3H)8.30-8.39(m，1H) ESI(Pos)339 (M+H) + 88-89
12 1H NMR(600MHz，CHLOROFORM-d)d ppm 0.44-0.72(m，4H)0.74-0.90(m， 2H)1.84-2.05(m，1H)3.57-3.85(m，2H)6.43-6.57(m，1H)7.22-7.38(m， 1H)7.64-7.85(m，3H)8.42-8.55(m，1H)8.70-8.83(m，10H) ESI(Pos)353 (M+H) + 93-94
13 1H NMR(200MHz，CHLOROFORM-d)d ppm -0.00-0.53(m，4H)0.54-0.77(m， 1H)1.81(q，J＝7.0Hz，2H)4.43(t，J＝7.0Hz，2H)6.58-6.69(m，1H)7.18-7.31 (m，1H)7.55-7.71(m，3H)8.14-8.27(m，1H)8.40-8.51(m，1H) ESI(Pos)353 (M+H) + 56-58
14 1H NMR(200MHz，CHLOROFORM-d)d ppm 1.12(t，J＝7.03Hz，3H)3.44(q， J＝7.03Hz，2H)3.84(t，J＝4.83Hz，2H)4.54(t，J＝4.83Hz，2H)6.56-6.69(m，1 H)7.18-7.31(m，1H)7.57-7.77(m，3H)8.13-8.26(m，1H)8.41-8.50(m，1 H) ESI(Pos)357 (M+H) + 104.5-105.5
15 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.77(m，4H)1.32-1.51(m， 1H)4.19(d，J＝7.5Hz，2H)7.20-7.31(m，1H)7.57-7.71(m，2H)7.81-7.87 (m，1H)8.14-8.26(m，1H)8.35-8.43(m，1H) ESI(Pos)439 (M+Na) + 124-126
16 1H NMR(200MHz，CHLOROFORM-d)d ppm 3.21(t，J＝7.3Hz，2H)4.54(t，J＝7.3 Hz，2H)6.43-6.55(m，1H)7.10-7.36(m，7H)7.54-7.73(m，2H)8.19-8.32 (m，1H)8.45-8.57(m，1H) ESI(Pos)389 (M+H) + 117-118
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
17 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.59-0.73(m，2H)1.26-1.46(m， 1H)4.13(d，J＝7.47Hz，2H)6.62-6.74(m，1H)7.02-7.17(m，1H)7.39-7.50 (m，1H)7.58-7.77(m，3H)8.30-8.41(m，1H) ESI(Pos)339 (M+H) + 88.5-89
18 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.56(m，2H)0.56-0.75(m， 2H)1.34-1.56(m，1H)4.22(d，J＝7.03Hz，2H)6.59-6.74(m，1H)7.10-7.28 (m，1H)7.53-7.79(m，3H)8.29-8.53(m，2H) ESI(Pos)339 (M+H) + 127-127.5
19 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.39-0.51(m，2H)0.60-0.72(m， 2H)1.33-1.55(m，1H)3.94(s，3H)4.16(d，J＝7.03Hz，2H)6.55-6.66(m，1H) 6.95-7.05(m，1H)7.52-7.72(m，3H)8.09-8.14(m，1H)8.36-8.46(m，1H) ESI(Pos)351 (M+H) + -
20 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.36-0.72(m，4H)1.34-1.58(m， 1H)3.80(s，3H)3.85(s，3H)4.15(d，J＝7.5Hz，2H)6.48-6.61(m，1H)6.84- 6.93(m，2H)7.40-7.46(m，1H)7.46-7.59(m，1H)7.60-7.69(m，1H)8.27- 8.38(m，1H) ESI(Pos)313 (M+H) + -
21 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.74(m，4H)1.34-1.54(m， 1H)4.20(d，J＝7.0Hz，2H)6.65-6.77(m，1H)7.51-7.62(m，1H)7.63-7.80 (m，3H)7.84-7.91(m，1H)8.09-8.17(m，1H)8.49-8.59(m，1H)8.81-8.90 (m，1H)8.94-9.01(m，1H) ESI(Pos)304 (M+H) + -
22 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.77(m，4H)1.30-1.48(m， 1H)2.38(s，3H)4.23(d，J＝7.0Hz，2H)6.79-6.91(m，1H)7.19-7.31(m，1H) 7.55-7.69(m，2H)7.75-7.84(m，1H)8.05-8.18(m，1H) ESI(Pos)353 (M+H) + -
23 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.36-0.51(m，2H)0.56-0.71(m， 2H)1.32-1.52(m，1H)2.36(s，3H)4.18(d，J＝7.0Hz，2H)6.48-6.56(m，1H) 7.18-7.30(m，1H)7.56-7.67(m，2H)8.14-8.31(m，2H) ESI(Pos)353 (M+H) + 81-83
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
24 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.37-0.73(m，4H)1.30-1.55(m， 1H)2.25(s，3H)4.21(d，J＝7.5Hz，2H)7.17-7.31(m，1H)7.44-7.69(m，2H) 8.10-8.27(m，1H)8.35-8.48(m，1H) ESI(Pos)353 (M+H) + 118-120
25 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.49-0.62(m，4H)1.20-1.40(m， 1H)2.61(s，3H)4.50(d，J＝7.0Hz，2H)6.54(d，J＝7.0Hz，1H)7.19-7.30(m，1 H)7.45-7.67(m，2H)8.11-8.31(m，2H) ESI(Pos)353 (M+H) + 96-98
26 1H NMR(600MHz，CHLOROFORM-d)d ppm 0.39-0.45(m，2H)0.67-0.73(m， 2H)1.31-1.39(m，1H)4.10(d，J＝7.34Hz，2H)7.47(t，J＝7.79Hz，1H)7.57(t， J＝7.57Hz，1H)7.65(dd，J＝9.40，2.06Hz，1H)7.68(d，J＝7.79Hz，1H)7.76(d， J＝7.79Hz，1H)8.02(s，1H)8.27(d，J＝9.17Hz，1H) APCI(Pos)389 (M+H) + 93-93.5
27 1H NMR(600MHz，CHLOROFORM-d)d ppm 0.46-0.54(m，2H)0.72-0.80(m， 2H)1.44-1.51(m，1H)4.22(d，J＝7.34Hz，2H)7.56(t，J＝7.79Hz，1H)7.64 (dd，J＝9.63，2.29Hz.1H)7.73(d，J＝7.79Hz，1H)8.02(s.1H)8.33(d，J＝9.63Hz， 1H)8.41(d，J＝7.79Hz.1H)8.51(s，1H) APCI(Pos)389 (M+H) + 84-85
28 1H NMR(600MHz，CHLOROFORM-d)d ppm -1.19- -1.12(m，2H)-0.78- -0.72 (m，2H)-0.14--0.04(m，1H)3.46(d，J＝9.2Hz，2H)6.92-6.97(m，1H)7.29- 7.34(m，1H)7.75-7.82(m，1H)8.35-8.43(m，2H)8.60-8.64(m，1H) ESI(Pos)407 (M+H) + -
29 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.77(m，4H)1.37-1.52(m， 1H)4.22(d，J＝7.5Hz，2H)6.68-6.77(m，1H)7.21-7.33(m，1H)7.61-7.74 (m，1H)7.78-7.88(m，1H)8.16-8.30(m，1H)8.65-8.73(m，1H) ESI(Pos)407 (M+H) + 85-86
30 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.77(m，4H)1.30-1.48(m， 1H)2.38(s，3H)4.23(d，J＝7.0Hz，2H)6.79-6.91(m，1H)7.19-7.31(m，1H) 7.55-7.69(m，2H)7.75-7.84(m，1H)8.05-8.18(m，1H) ESI(Pos)353 (M+H) + -
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
31 1H NMR(600MHz，CHLOROFORM-d)d ppm 0.42-0.53(m，2H)0.66-0.79(m， 2H)1.37-1.48(m，1H)4.20(d，J＝7.34Hz，2H)7.18-7.23(m，1H)7.65-7.70 (m，2H)8.03(s，1H)8.36(dd，J＝6.65，2.52Hz，1H)8.39(d，J＝9.63Hz，1H) APCI(Pos)407 (M+H) + 109-110
32 1H NMR(500MHz，CHLOROFORM-d)d ppm 0.36-0.70(m，4H)1.26-1.37(m， 1H)4.30(d，J＝6.9Hz，2H)6.97-7.03(m，1H)7.17-7.22(m，1H)7.22-7.26 (m，1H)7.54-7.59(m，1H)7.59-7.64(m，1H)7.66-7.72(m，1H) ESI(Pos)407 (M+H) + -
33 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.74(m，4H)1.30-1.49(m， 1H)4.17(d，J＝7.0Hz，2H)6.61-6.68(m，1H)7.22-7.32(m，1H)7.59-7.72 (m，2H)8.15-8.26(m，1H)8.51-8.56(m，1H) ESI(Pos)395 (M+Na) + 91-93
34 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.79(m，4H)1.33-1.52(m， 1H)4.20(d，J＝7.5Hz，2H)7.18-7.30(m，1H)7.51-7.71(m，2H)7.72-7.79 (m，1H)8.13-8.26(m，1H)8.39-8.51(m，1H) ESI(Pos)373 (M+H) + 117-119
35 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.48-0.67(m，4H)1.35-1.55(m， 1H)4.67(d，J＝7.5Hz，2H)6.70-6.76(m，1H)7.20-7.31(m，1H)7.42-7.54 (m，1H)7.59-7.70(m，1H)8.12-8.23(m，1H)8.25-8.35(m，1H) ESI(Pos)373 (M+H) + 81-83
36 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.83(m，4H)1.32-1.51(m， 1H)4.19(d，J＝7.5Hz，2H)7.21-7.33(m，1H)7.59-7.74(m，2H)7.99-8.07 (m，1H)8.15-8.28(m，1H)8.30-8.40(m，1H) ESI(Pos)407 (M+H) + 93-94
37 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.54(m，2H)0.64-0.80(m， 2H)1.31-1.51(m，1H)4.23(d，J＝7.5Hz，2H)7.48-7.78(m，3H)8.13-8.27 (m，1H)8.49-8.63(m，1H) ESI(Pos)357 (M+H) + 89-91
38 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.43-0.57(m，2H)0.60-0.77(m， 2H)1.39-1.58(m，1H)4.31(d，J＝7.0Hz，2H)7.19-7.32(m，1H)7.35-7.55 (m，5H)7.57-7.71(m，1H)7.83-7.98(m，2H)8.15-8.30(m，1H)8.46-8.61 (m，1H) ESI(Pos)415 (M+H) + 115-116
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
39 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.54(m，4H)1.28-1.51(m， 1H)4.02(s，3H)4.46(d，J＝7.5Hz，2H)6.03-6.09(m，1H)7.17-7.29(m，1H) 7.52-7.66(m，2H)7.99-8.09(m，1H)8.12-8.25(m，1H) ESI(Pos)369 (M+H) + 126-128
40 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.32-0.54(m，4H)1.41-1.58(m， 1H)2.73(s，6H)4.49(d，J＝6.6Hz，2H)6.33-6.42(m，1H)7.18-7.29(m，1H) 7.49-7.67(m，2H)8.06-8.25(m，2H) ESI(Pos)382 (M+H) + -
41 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.53-0.63(m，4H)1.12-1.37(m， 1H)2.78(s，3H)4.61(d，J＝7.0Hz，2H)7.25(d，1H)7.56-7.73(m，2H)8.05- 8.26(m，2H) ESI(Pos)431 (M+H) + 135-137
42 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.83(m，4H)1.24-1.45(m， 1H)4.16(d，J＝7.0Hz，2H)7.19-7.42(m，2H)7.61-7.71(m，2H)8.13-8.24 (m，1H) ESI(Pos)397 (M+Na) + 69-71
43 1H NMR(200MHz，CHLOROFORM-d)d ppm 2.23(s，3H)2.43(s，3H)3.81(s，3 H)3.83(s，3H)3.89(s，3H)6.22-6.27(m，1H)6.40-6.53(m，2H)7.93-8.01 (m，2H) ESI(Pos)301 (M+H) + 117.5-118
44 1H NMR(200MHz，CHLOROFORM-d)d ppm 2.27(s，3H)2.46(s，3H)2.63(s，3 H)4.97-5.30(m，4H)5.89-6.12(m，1H)6.27(s，1H)7.11-7.32(m，3H)7.86 -7.95(m，1H)8.02(s，1H) ESI(Pos)281 (M+H) + -
45 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.50-0.60(m，4H)1.15-1.37(m， 1H)2.30(s，3H)2.56(s，3H)4.46(d，J＝7.0Hz，2H)6.34-6.44(m，1H)7.16- 7.28(m，1H)7.54-7.67(m，1H)8.09-8.24(m，2H) ESI(Pos)367 (M+H) + 114-115
46 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.52-0.62(m，4H)1.14-1.30(m， 1H)2.43(s，3H)2.83(s，3H)4.63(d，J＝6.6Hz，2H)7.18-7.29(m，1H)7.56- 7.68(m，1H)8.09-8.22(m，1H)8.28(s，1H) ESI(Pos)445 (M+H) + 121-122
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
47 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.48-0.73(m，4H)1.23-1.49(m， 1H)4.71(d，J＝7.0Hz，2H)7.20-7.45(m，2H)7.62-7.90(m，5H)8.03-8.26 (m，2H) ESI(Pos)411 (M+Na) + 125-126
48 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.76(m，4H)1.33-1.52(m， 1H)4.23(d，J＝7.0Hz，2H)7.06-7.13(m，1H)7.26-7.37(m，1H)7.55-7.82 (m，5H)8.21-8.39(m，2H) ESI(Pos)389 (M+H) + -
49 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.27-0.55(m，4H)1.22-1.44(m， 1H)4.19(d，J＝7.0Hz，2H)6.91-6.99(m，1H)7.18-7.32(m，1H)7.51-7.82 (m，2H)8.34-8.43(m，2H) ESI(Pos)340 (M+H) + -
50 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.28-0.40(2H，m)，0.57-0.69(2 H，m)，1.21-1.39(1H，m)，3.98(2H，d，J＝7.47Hz)，6.54-6.64(2H，m)，7.45- 7.73(4H，m)，7.76-7.84(1H，m)8.38-8.46(1H，m) ESI(Pos)356 (M+H) + -
51 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.69(m，4H)1.19-1.33(m，1 H)1.37(s，9H)4.12(d，J＝7.0Hz，2H)7.17(s，1H)7.18-7.28(m，1H)7.57- 7.68(m，1H)8.12-8.23(m，1H) ESI(Pos)342 (M+H) + -
52 1H NMR(200MHz CHLOROFORM-d)d ppm 0.56-0.69(m，4H)1.20-1.37(m， 1H)1.42(d，J＝6.6Hz，6H)3.13-3.31(m，1H)4.24(d，J＝7.0Hz，2H)7.26- 7.39(m，1H)7.67-7.80(m，1H)8.27-8.40(m，1H) ESI(Pos)388 (M+H) + -
53 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.73(m，4H)1.17-1.41(m， 1H)1.36(s，9H)4.17(d，J＝7.0Hz，2H)7.17(s，1H)7.46-7.57(m，1H)7.65- 7.73(m，1H)8.38-8.46(m，1H)8.48-8.57(m，1H) ESI(Pos)367 (M+H) + -
54 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.70(m，4H)1.21-1.32(m， 1H)1.36(s，9H)4.13(d，J＝7.0Hz，2H)7.11-7.23(m，1H)7.19(s，1H)7.56- 7.67(m，1H)8.29-8.37(m，1H) ESI(Pos)385 (M+H) + -
Table 8 (continuing)
Compound N o. 1H-NMR Mass Fusing point (℃)
55 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.69(m，4H)1.20-1.34(m， 1H)1.35(s，9H)3.93(s，3H)4.09(d，J＝7.5Hz，2H)6.95-7.03(m，1H)7.23(s， 1H)7.54-7.62(m，1H)8.05-8.12(m，1H) ESI(Pos)397 (M+H) + 64-65
56 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.55(m，2H)0.67-0.81(m， 2H)1.20-1.35(m，1H)1.43(s，9H)4.01(d，J＝7.0Hz，2H)7.16-7.32(m，1H) 7.56-7.70(m，1H)7.85(s，1H)8.16-8.29(m，1H) ESI(Pos)401 (M+H) + 85-87
57 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.58(m，2H)0.68-0.83(m， 2H)1.21-1.38(m，1H)1.43(s，9H)4.05(d，J＝7.5Hz，2H)7.52(t，J＝7.5Hz，1 H)7.69(d，J＝7.5Hz，1H)7.86(s，1H)8.46(d，J＝7.5Hz，1H)8.57(s，1H) ESI(Pos)383 (M+H) + 54-55
58 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.67-0.80(m，2H)1.19-1.38(m， 1H)1.43(s，9H)4.02(d，J＝7.0Hz，2H)7.09-7.28(m，1H)7.55-7.68(m，1H) 7.88(s，1H)8.33-8.43(m，1H) ESI(Pos)401 (M+H) + 63-65
59 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.53(m，52H)0.64-0.80(m， 2H)1.18-1.36(m，1H)1.42(s，9H)3.94(s，3H)3.97(d，J＝7.5Hz，2H)6.95- 7.05(m，1H)7.52-7.63(m，1H)7.91(s，1H)8.11-8.17(m，1H) ESI(Pos)413 (M+H) + 95-97
Table 9
Compound N o. H-NMR Fusing point (℃)
60 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.33-0.84(m，4H)1.14-1.50(m，1H) 4.15(d，J＝7.5Hz，2H)6.76(d，J＝4.8Hz，1H)7.12-7.39(m，2H)7.63- 7.75(m，1H)8.26-8.39(m，1H) 96-97
61 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.16(t，J＝7.0Hz，3H)，3.49(q，J＝7.0 Hz，2H)，3.81(t，J＝4.8Hz，2H)，4.47(t，J＝4.8Hz，2H)，6.70(d，J＝4.4Hz， 1H)，7.17-7.36(m，2H)，7.62-7.76(m，1H)，8.25-8.37(m，1H) 199-201
62 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.41(t，J＝7.0Hz，3H)，2.38(s，3H)， 4.32(q，J＝7.0Hz，2H)，6.36(s，1H)，7.27(t，J＝7.7Hz，1H)，7.68(t， J＝7.7Hz，1H)，8.33(t，J＝7.7Hz，1H) 48-50
63 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.73(m，4H)，1.13-1.42(m，1H) 2.41(s，3H)4.20(d，J＝7.0Hz，2H)6.38(s，1H)7.21-7.33(m，1H)7.63 -7.74(m，1H)8.26-8.36(m，1H) 109-111
64 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.33(s，3H)，3.81(s，3H)，6.71(s，1 H)，7.32-7.45(m，1H)，8.51-8.59(m，1H)，8.65-8.74(m，1H)，9.51- 9.59(m，4H) 173-174
65 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.47(t，J＝7.0Hz，3H)，2.35(s，3H)， 4.35(q，J＝7.0Hz，2H)，6.78(s，1H)，7.29(t，J＝7.7Hz，1H)，7.69(t， J＝7.7Hz，1H)，8.30(t，J＝7.7Hz，1H) 90-92
66 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.77(m，4H)，1.18-1.43(m，1 H)，2.35(s，3H)，4.11(d，J＝7.5Hz，2H)，6.84(s，1H)，7.31-7.42(m，1 H)，8.47-8.56(m，1H)，8.62-8.74(m，1H)，9.48-9.54(m，1H) 115-117
67 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.76(m，4H)1.18-1.42(m，1H) 2.32-2.39(m，3H)4.08(d，J＝7.0Hz，2H)6.83-6.89(m，1H)7.19-7.34 (m，1H)7.60-7.75(m，1H)8.22-8.37(m，1H) 129-130
68 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.26(s，6H)3.82(s，3H)7.55(t， J＝7.9Hz，1H)7.71(d，J＝7.9Hz，1H)8.50(d，J＝7.9Hz，1H)8.61(s，1H) 110-111
69 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.26(s，6H)3.78(s，3H)7.21-7.33 (m，1H)7.62-7.72(m，1H)8.28-8.39(m，1H) 182-183
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
70 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)2.26(s，3H) 2.26(s，3H)4.30(q，J＝7.0Hz，2H)7.16-7.35(m，1H)7.55-7.76(m，1 H)8.14-8.47(m，1H) 198-200
71 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.61(m，4H)1.22-1.33(m，1H) 1.26(t，J＝7.5Hz，3H)2.24(s，3H)2.27(s，3H)3.11(q，J＝7.5Hz，2H) 4.14(d，J＝6.8Hz，2H)7.19-7.27(m，2H)7.30-7.37(m，1H)7.97-8.02 150-152
72 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.65(m，4H)，1.18-1.41(m，1 H)，2.26(s，3H)，2.29(s，3H)，4.21(d，J＝7.0Hz，2H)，7.54(t，J＝7.9Hz， 1H)，7.70(d，J＝7.9Hz，1H)，8.44(d，J＝7.9Hz，1H)，8.56(s，1H) 197-199
73 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.60(m，4H)1.21-1.37(m，1H) 2.23(s，3H)2.26(s，3H)2.34(s，3H)2.69(s，3H)4.15(d，J＝7.0Hz，2 H)7.02-7.08(m，2H)8.03-8.08(m，1H) 145-148
74 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.60(m，4H)，1.22-1.33(m，1 H)，2.26(s，3H)，2.28(s，3H)，4.16(d，J＝7.0Hz，2H)，7.18-7.25(m，1 H)，7.29-7.38(m，1H)，7.59-7.66(m，1H)，7.87-7.94(m，1H) 125-127
75 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)，1.20-1.35(m，1 H)，2.25(s，3H)，2.28(s，3H)，4.15(d，J＝6.8Hz，2H)，7.23-7.34(m，2 H)，7.37-7.44(m，1H)，7.90-8.00(m，1H) 125-127
76 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.43-0.58(m，4H)，1.18-1.29(m，1 H)，2.25(s，3H)，2.28(s，3H)，4.12(d，J＝7.0Hz，2H)，7.43-7.52(m，1 H)，7.52-7.61(m，1H)，7.67-7.74(m，1H)，7.81-7.87(m，1H) 114-116
77 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.64(m，4H)，1.21-1.36(m，1 H)，2.26(s，3H)，2.29(s，3H)，4.20(d，J＝7.0Hz，2H)，7.26-7.35(m，1 H)，7.55-7.61(m，1H)，8.17-8.22(m，1H)，8.40-8.43(m，1H) 159-160
78 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)，1.21-1.35(m，1 H)，2.25(s，3H)，2.28(s，3H)，4.18(d，J＝6.8Hz，2H)，7.69-7.06(m，1 H)，7.33-7.40(m，1H)，7.88-7.99(m，2H) 130-132
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
79 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.22-1.32(m，1 H)，2.26(s，3H)，2.29(s，3H)，4.18(d，J＝7.1Hz，2H)7.06-7.16(m，1 H)，7.41-7.50(m，1H)，7.94-8.03(m，1H) 109-111
80 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)，1.21-1.32(m，1 H)，2.26(s，3H)，2.28(s，3H)，4.16(d，J＝7.0Hz，2H)，6.97-7.07(m，1 H)，7.32-7.41(m，1H)，7.63-7.72(m，1H) 139-140
81 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.61(m，4H)，1.21-1.31(m，1 H)，2.26(s，3H)，2.29(s，3H)，4.15(d，J＝7.0Hz，2H)，7.24-7.31(m，1 H)，7.41-7.46(m，1H)，7.90-7.97(m，1H) 57-58
82 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.61(m，4H)，1.14-1.38(m，1H) 2.26(s，3H)2.29(s，3H)4.15(d，J＝7.0Hz，2H)7.22-7.37(m，2H)7.90 -7.94(m，1H) 113-115
83 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.59(m，4H)，1.18-1.32(m，1 H)，2.26(s，3H)，2.29(s，3H)，4.17(d，J＝6.8Hz，2H)，7.26-7.35(m，2 H)，7.96-8.06(m，1H) 154-155
84 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.60(m，4H)，1.19-1.34(m，1 H)，2.25(s，3H)，2.28(s，3H)，4.16(d，J＝7.0Hz，2H)，6.98-7.11(m，1 H)7.32-7.41(m，1H)7.94-8.05(m，1H) 144-146
85 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.63(m，4H)1.19-1.33(m，1H) 2.26(s，3H)2.29(s，3H)4.16(d，J＝7.0Hz，2H)7.21-7.29(m，1H)7.85 -7.94(m，1H) 161-163
86 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)，1.26(s，1H)， 2.26(s，3H)，2.29(s，3H)，4.15(d，J＝7.0Hz，2H)，7.44-7.51(m，1H)， 7.78-7.85(m，1H) 59-60
87 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.44-0.58(m，4H)，1.14-1.33(m，1 H)，2.25(s，3H)，2.28(s，3H)，4.15(d，J＝7.0Hz，2H)，7.28-7.48(m，3 H)，8.06(dd，J＝7.5，1.8Hz，1H)
88 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.60(m，4H)，1.20-1.35(m，1 H)，2.24(s，3H)，2.27(s，3H)，3.81(s，3H)，3.87(s，3H)，4.14(d，J＝7.0 Hz，2H)，6.88-6.97(m，2H)，7.56-7.61(m，1H) 124-126
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
89 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)，1.20-1.36(m，1 H)，2.25(s，3H)，2.28(s，3H)，2.64-2.67(m，3H)，4.16(d，J＝6.9Hz，2 H)，6.95-7.05(m，1H)，7.11-7.20(m，1H)，7.77-7.86(m，1H) 82-84
90 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.61(m，4H)1.20-1.34(m，1 H)，2.24(s，3H)，2.28(s，3H)，2.69(s，3H)，4.14(d，J＝6.8Hz，2H)，7.18 -7.23(m，2H)，8.03-8.10(m，1H) 124-125
91 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.60(m，4H)1.20-1.34(m，1H) 2.24(s，3H)2.27(s，3H)2.35(s，3H)4.16(d，J＝7.0Hz，2H)7.11-7.17 (m，1H)7.45-7.47(m，1H)7.85-7.90(m，1H) 90-92
92 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.61(m，4H)，1.20-1.32(m， 1 H)，2.27(s，3H)，2.30(s，3H)，4.19(d，J＝7.1Hz，2H)，7.16-7.25(m，1 H)，7.62-7.69(m，1H)，8.41-8.48(m，1H) 122-123
93 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.42-0.59(m，4H)，1.17-1.28(m，1 H)，2.26(s，3H)，2.29(s，3H)，4.12(d，J＝7.0Hz，2H)，7.10-7.19(m，1 H)，7.51-7.59(m，1H)，7.66-7.74(m，1H) 131-133
94 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.40-0.55(m，4H)，1.13-1.24(m，1 H)，2.26(s，3H)，2.28(s，3H)，4.07(d，J＝7.0Hz，2H)，7.23-7.31(m，1 H)，7.35-7.48(m，2H) 111-113
95 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.43-0.59(m，4H)，1.15-1.30(m，1 H)，2.26(s，3H)，2.28(s，3H)，4.12(d，J＝7.1Hz，2H)，7.20-7.30(m，1 H)，7.37-7.45(m，1H)，7.88-7.97(m，1H) 143-144
96 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.61(m，4H)，1.20-1.34(m，1 H)，2.24(s，3H)，2.27(s，3H)，3.89(s，3H)，4.14(d，J＝7.0Hz，2H)，6.86 -6.94(m，1H)，7.02-7.11(m，1H)，7.66-7.74(m，1H) 107-109
97 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.59(m，4H)1.19-1.34(m，1 H)，2.24(s，3H)，2.27(s，3H)，3.89(s，3H)，4.14(d，J＝7.0Hz，2H)，6.86 -6.93(m，1H)，7.27-7.35(m，1H)，7.91-7.96(m，1H) 121-123
98 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.54(m，4H)，0.87(t，J＝7.5Hz， 6H)，1.11-1.22(m，1H)，1.45-1.78(m，4H)，2.19(s，3H)，2.23(s，3 H)，2.25-2.35(m，1H)，4.06(d，J＝7.0Hz，2H) 67-69
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
99 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.56(m，4H)0.91(s，9H)0.97 (d，J＝6.4Hz，3H)1.07-1.37(m，4H)2.19(s，3H)2.21-2.55(m，2H) 2.23(s，3H)4.05(d，J＝7.2Hz，2H) 42-43
100 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.45-0.57(m，4H)1.09-1.29(m，4H) 1.44-1.68(m，3H)1.74-1.89(m，2H)2.19(s，3H)2.23(s，3H)2.27- 2.44(m，1H)2.45-2.52(m，2H)4.04(d，J＝7.0Hz，2H) 108-109
101 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.58(m，4H)，1.11-1.22(m，1 H)，2.29(s，3H)，2.32(s，3H)，4.13(d，J＝7.0Hz，2H) 92-94
102 1H NMR(300MHz CHLOROFORM-D)d ppm 0.35-0.51(m，4H)0.90(t，J＝7.3Hz，3 H)1.01-1.16(m，1H)1.79-2.31(m，2H)2.17(s，3H)2.20(s，3H)3.59 (t，J＝7.7Hz，1H)4.00(d，J＝7.2Hz，2H)7.13-7.20(m，1H)7.22-7.30 (m，2H)7.33-7.44(m，2H) 108-110
103 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.25(s，3H)2.28(s，3H)3.33(s，3H) 3.81(t，J＝5.3Hz，2H)4.42(t，J＝5.3Hz，2H)7.54(t，J＝7.5Hz，1H)7.71 (d，J＝7.5Hz，1H)8.46(d，J＝7.5Hz，1H)8.56(s，1H) 64-66
104 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.25(s，3H)2.28(s，3H)3.31(s，3H) 3.79(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz，2H)7.09-7.38(m，1H)7.53- 7.82(m，1H)8.16-8.39(m，1H) 182-183
105 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.01-2.19(m，2H)，2.26(s，6H)， 3.33(s，3H)，3.43(t，J＝5.7Hz，2H)，4.31(t，J＝5.7Hz，2H)，7.20-7.33 (m，1H)，7.60-7.75(m，1H)，8.25-8.40(m，1H) 104-106
106 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.15(t，J＝7.0Hz，3H)2.26(s，3H) 2.29(s，3H)3.48(d，J＝7.0Hz，2H)3.84(t，J＝5.5Hz，2H)4.42(t，J＝5.5 Hz，2H)7.54(t，J＝7.5Hz，1H)7.71(d，J＝7.5Hz，1H)8.46(d，J＝7.5Hz，1 138-140
107 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.13(t，J＝6.7Hz，3H)2.26(s，3H) 2.29(s，3H)3.45(q，J＝6.7Hz，2H)3.82(t，J＝5.3Hz，2H)4.37(t，J＝5.3 Hz，2H)7.10-7.37(m，1H)7.51-7.81(m，1H)8.06-8.42(m，1H) 147-148
108 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.25(t，J＝7.6Hz，3H)，1.40(t，J＝7.1 Hz，3H)，2.27(s，3H)，2.67(q，J＝7.6，0.5Hz，2H)，4.30(q，J＝7.1Hz，2 H)，7.22-7.30(m，1H)，7.63-7.70(m，1H)，8.27-8.35(m，1H) 115-117
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
109 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.60(m，4H)，1.18-1.36(m，1 H)，1.27(t，J＝7.5Hz，3H)，2.30(s，3H)，2.68(q，J＝7.5Hz，2H)，4.19(d， J＝7.1Hz，2H)，7.27(t，J＝7.0Hz，1H)，7.67(t，J＝7.0Hz，1H)，8.29(t， 164-166
110 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.29(d，J＝6.6Hz，6H)2.27(s，3H) 3.08-3.28(m，1H)3.78(s，3H)7.21-7.33(m，1H)7.62-7.72(m，1H) 7.21-7.33(m，1H) 89-91
111 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.29(d，J＝7.0Hz，6H) 1.40(t，J＝7.0 Hz，3H)2.28(s，3H)3.02-3.31(m，1H)4.30(q，J＝7.0Hz，2H)7.20- 7.32(m，1H)7.67-7.71(m，1H)8.26-8.36(m，1H) 64-66
112 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.69(m，4H)1.09-1.42(m，1H) 1.30(d，J＝7.0Hz，6H)2.32(s，3H)3.06-3.31(m，1H)4.22(d，J＝7.0Hz， 2H)7.55(t，J＝7.5Hz，1H)7.70(d，J＝7.5Hz，1H)8.44(d，J＝7.5Hz，1H) 89-91
113 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，4H)1.15-1.38(m，1H) 1.30(d，J＝7.0Hz，6H)2.32(s，3H)3.09-3.27(m，1H)4.19(d，J＝7.0Hz， 2H)7.19-7.34(m，1H)7.58-7.73(m，1H)8.20-8.36(m，1H) 64-66
114 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.29(d，J＝7.0Hz，6H)2.30(s，3H) 3.07-3.26(m，1H)3.32(s，3H)3.79(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz， 2H)7.20-7.32(m，1H)7.61-7.72(m，1H)8.23-8.34(m，1H) 132-134
115 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.12(dd，J＝7.0Hz，3H)1.29(d，J＝6.6 Hz，6H)2.31(s，3H)3.09-3.26(m，1H)3.45(q，J＝7.0Hz，2H)3.82(t， J＝5.3Hz，2H)4.38(t，J＝5.3Hz，2H)7.20-7.32(m，1H)7.62-7.72（m，1 H)8.23-8.34(m，1H) 96-97
116 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.38(s，3H)2.71(s，3 H)，3.75(s，3H)，7.17-7.35(m，3H)，8.08-8.19(m，1H) 173-175
117 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.71(s，3H) 7.40-7.62(m，2H)7.67-7.75(m，1H)7.84-7.92(m，1H) 74-76
118 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.40(s，3H)，3.81(s，3 H)，7.43-7.80(m，2H)，8.38-8.68(m，2H) 140-142
119 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.76(s，3H) 7.20-7.36(m，2H)7.37-7.48(m，1H)7.91-8.04(m，1H) 119-121
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
120 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.76(s，3H) 7.15-7.39(m，1H)7.58-7.67(m，1H)7.90-7.99(m，1H) 182-184
121 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.39(s，3H)，3.79(s，3 H)，7.20-7.43(m，1H)，7.54-7.63(m，1H)，8.17-8.29(m，1H)，8.42- 8.52(m，1H) 173-175
122 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(8.9H)2.39(s，3H)3.79(s，3H) 6.98-7.10(m，1H)7.31-7.43(m，1H)7.91-7.99(m，2H) 83-85
123 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.39(s，3H)，3.74(s，3 H)，7.22-7.51(m，3H)，8.06-8.17(m，1H)
124 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.38(s，3H)，3.00(s，6 H)，3.79(s，3H)，6.81-6.91(m，1H)，7.24-7.35(m，1H)，7.70-7.80(m， 189-190
125 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)，2.42(s，3H)，3.82(s，3 H)，7.47-7.59(m，1H)，7.67-7.78(m，1H)，8.46-8.55(m，1H)，8.62- 8.68(m，1H) 131-133
126 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.83(s，3H) 3.94(s，3H)7.50(t，J＝7.9Hz，1H)8.07-8.21(m，1H)8.44-8.58(m，1 H)8.99(t，J＝1.5Hz，1H) 192-193
127 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)2.41(s，3H)3.84(s，3H) 7.55(t，J＝7.9Hz，1H)8.20(d，J＝7.9Hz，1H)8.55(d，J＝7.9Hz，1H)9.07 250-252
128 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.40(s，3H)，3.77(s，3 H)，7.04-7.28(m，2H)，7.88(t，J＝6.8Hz，1H) 176-178
129 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.78(s，3H) 7.05-7.17(m，1H)7.39-7.52(m，1H)7.95-8.07(m，1H) 203-205
130 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H) 6.95-7.09(m，1H)7.31-7.43(m，1H)7.68-7.78(m，1H) 125-126
131 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H) 6.88-7.02(m，1H)7.52-7.63(m，1H)7.65-7.75(m，1H) 161-162
132 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)2.40(s，3H)3.77(s，3H) 6.93-7.06(m，1H)7.43-7.54(m，1H)8.23-8.32(m，1H) 144-145
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
133 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H) 2.40(s，3H)3.76(s，3H) 7.21-7.39(m，2H)7.96-8.01(m，1H) 171-173
134 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.72(s，3H) 6.72-6.94(m，1H)6.98-7.21(m，1H) 143-145
135 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H) 7.19-7.31(m，1H)7.88-8.02(m，1H) 145-146
136 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H) 7.44-7.51(m，1H)，7.83-7.92(m，1H) 205-207
137 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)，2.45(s，3H)，3.46(s，3 H)，3.80(s，3H)，3.85(s，3H)，6.46-6.60(m，2H)，7.30(s，1H) 138-140
138 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)2.66(s，3H) 3.76(s，3H)6.92-7.06(m，1H)7.10-7.21(m，1H)7.81-7.92(m，1H) 145-146
139 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)2.66(s，3H) 3.73(s，3H)7.09-7.20(m，1H)7.35-7.44(m，1H)7.77-7.85(m，1H) 161-162
140 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)2.68(s，3H) 3.73(s，3H)7.01-7.12(m，1H)7.54-7.62(m，1H)7.79-7.87(m，1H) 143-144
141 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.40(s，3H)，3.78(s，3 H)，7.21-7.32(m，1H)，7.66(t，J＝6.4Hz，1H)，8.31(t，J＝6.6Hz，1H) 176-178
142 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.41(s，3H)，3.78(s，3 H)，7.15-7.29(m，1H)，7.60-7.70(m，1H)，8.46(dd，J＝6.6，1.8Hz，1H) 140-142
143 1H NMR(200NHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.72(s，3H) 7.05-7.23(m，1H)7.55-7.65(m，1H)7.65-7.76(m，1H) 83-85
144 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.24(s，3H)2.38(s，3H) 3.71(s，3H)6.73-6.86(m，1H)6.98-7.20(m，1H) 140-142
145 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)2.39(s，3H)3.67(s，3H) 7.31-7.64(m，2H) 129-130
146 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.41(s，9H)2.38(s，3H)3.74(s，3H) 3.90(s，3H)6.85-6.94(m，1H)7.26-7.36(m，1H)7.96-8.02(m，1H) 177-179
147 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.41(s，9H)2.38(s，3H)3.74(s，3H) 3.91(s，3H)6.89-7.02(m，2H)7.96-8.05(m，1H) 117-119
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
148 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.46(s，9H)，2.46(s，3H)，3.85(s，3 H)，7.92-8.03(m，1H)，8.75(d，J＝5.7Hz，1H)，9.18(d，J＝7.9Hz，1H)， 202-203
149 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)2.41(s，3H)3.74(s，3H) 180-182
150 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.28(t，J＝7.7Hz，3H)，1.37(t，J＝7.3 Hz，3H)，1.43(s，9H)，2.40(s，3H)，3.14(q，J＝7.7Hz，2H)，4.28(q， J＝7.3Hz，2H)，7.17-7.38(m，3H)，7.98-8.08(m，1H)
151 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.34(t，J＝7.0Hz，3H)1.43(s，9H) 2.40(s，3H)4.26(q，J＝7.0Hz，2H)7.40-7.62(m，2H)7.67-7.75(m，1H) 7.84-7.92(m，1H) 74-76
152 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.36-1.52(m，12H)，2.42(s，3H) 4.35(q，J＝7.0Hz，2H)，7.38-7.85(m，2H)，8.32-8.70(m，2H) 158-160
153 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.35(t，J＝7.3Hz，3H)1.42(s，9H) 2.40(s，3H)4.30(q，J＝7.3Hz，2H)7.23-7.48(m，3H)8.06-8.15(m，1 104-105
154 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)1.42(s，9H) 2.41(s，3H)4.31(d，J＝7.0Hz，2H)6.92-7.06(m，1H)7.42-7.54(m，1 H)8.20-8.29(m，1H) 105-106
155 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.2Hz，3H)1.43(s，9H) 2.41(s，3H)4.30(q，J＝7.2Hz，2H)6.92-7.02(m，1H)7.52-7.63(m，1 H)7.63-7.74(m，1H) 115-116
156 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.0Hz，3H)1.43(s，9H) 2.41(s，3H)4.30(q，J＝7.0Hz，2H)6.98-7.11(m，1H)7.32-7.42(m，1 H)7.97-8.09(m，1H) 99-100
157 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.2Hz，3H)1.42(s，9H) 2.41(s，3H)4.30(q，J＝7.2Hz，2H)6.80-6.94(m，1H)7.60-7.72(m，1 H)8.38-8.47(m，1H) 87-89
158 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.2Hz，3H)1.43(s，9H) 2.42(s，3H)4.30(q，J＝7.2Hz，2H)7.23-7.31(m，1H)7.31-7.38(m，1 H)7.94-7.99(m，1H) 127-128
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
159 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.2Hz，3H)1.43(s，9H) 2.42(s，3H)4.29(q，J＝7.2Hz，2H)7.16-7.33(m，1H)7.86-8.00(m，1 107-108
160 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.1Hz，3H)1.43(s，9) 2.42(s，3H)，4.29(q，J＝7.1Hz，2H)，7.45-7.50(m，1H)，7.83-7.89(m， 112-114
161 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)1.43(s，9H) 2.41(s，H)2.67(s，3H)4.30(q，J＝7.0Hz，2H)6.92-7.06(m，1H)7.10- 7.21(m，1H)7.80-7.91(m，1H) 108-109
162 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.0Hz，3H)，1.42(s，9H) 2.40(s，3H)，2.70(s，3H)，4.29(q，J＝7.0Hz，2H)，7.15-7.24(m，2H)， 8.06-8.13(m，1H) 125-126
163 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.37(t，J＝7.3Hz，3H)1.42(s，9H) 2.34(s，3H)，2.40(s，3H)，4.30(q，J＝7.3Hz，2H)，7.09-7.17(m，1H)， 7.44-7.49(m，1H)，7.86-7.93(m，1H) 100-102
164 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.34(t，J＝7.2Hz，3H)1.43(s，9H) 2.41(s，3H)4.27(q，J＝7.2Hz，2H)7.07-7.21(m，1H)7.54-7.64(m，1 H)7.65-7.76(m，1H) 103-104
165 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)1.43(s，9H) 2.42(s，3H)4.32(q，J＝7.0Hz，2H)，7.20-7.32(m，1H)7.61-7.72(m，1 H)8.25-8.36(m，1H) 97-99
166 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.2Hz，3H)1.42(s，9H) 2.41(s，3H)4.30(q，J＝7.2Hz，2H)6.80-6.94(m，1H)7.60-7.72(m，1 H)8.38-8.47(m，1H) 113-115
167 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.37(t，J＝7.3Hz，3H)1.41(s，9H) 2.40(s，3H)3.90(s，3H)4.28(q，J＝7.3Hz，2H)6.85-6.94(m，1H)7.26 -7.36(m，1H)7.94-7.99(m，1H) 108-109
168 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.37(t，J＝7.0Hz，3H)，1.41(s，9H) 2.39(s，3H)，3.91(s，3H)，4.27(q，J＝7.0Hz，2H)，6.91-6.99(m，2H)， 7.96-8.03(m，1H)
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
169 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(t，J＝7.2Hz，3H)1.43(s，9H) 2.42(s，3H)4.35(q，J＝7.2Hz，2H)7.37(dd，J＝7.9，5.3Hz，1H)8.52(d， J＝7.9Hz，1H)8.67(d，J＝5.3Hz，1H)9.53(s，1H)
170 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.36(t，J＝7.2Hz，3H)1.44(s，9H) 2.42(s，3H)4.28(q，J＝7.2Hz，2H)7.59(d，J＝5.3Hz，1H)8.78(d，J＝5.3 Hz，1H)9.25(s，1H) 110-112
171 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.14-1.35(m，2H)1.30(t，J＝7.1H，3 H)1.38(s，9H)1.47-1.69(m，4H)1.77-1.90(m，2H)2.31-2.45(m，1 H)2.35(s，3H)2.48-2.53(m，2H)4.18(q，J＝7.1Hz，2H) 149-150
172 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.34(t，J＝7.1Hz，3H)，1.42(s，9H)， 2.42(s，3H)，4.27(q，J＝7.1Hz，2H) 113-115
173 1H NMR(200MHz，CHLOROFORM-d)d ppm 1.32-1.46(m，12H)2.42(s，3H)2.76 (s，3H)4.30(q，J＝7.3Hz，2H)7.26-7.35(m，1H)7.47-7.57(m，1H) 8.37-8.43(m，1H) 63-65
174 1H NMR(200MHz，CHLOROFORM-d)d ppm 1.37(t，J＝7.3Hz，3H)1.43(s，9H) 2.41(s，3H)4.29(q，J＝7.3Hz，2H)6.33-7.16(m，2H)7.46-7.56(m，1 H)8.17-8.21(m，1H) 95-97
175 1H NMR(200Hz，CHLOROFORM-D)d ppm 1.06(t.J＝7.5Hz，3H)，1.43(s，9H)， 1.73-1.96(m，2H)2.41(s，3H)4.24(t，J＝7.9Hz，2H)，7.54(t，J＝7.7 Hz，1H)，7.65-7.77(d，J＝7.7Hz，1H)，8.46(d，J＝7.7Hz，1H)，8.60(s，1 172-174
176 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，1.78(d，J＝6.6Hz，6H)， 2.41(s，3H)，4.48-4.87(m，1H)，7.55(t，J＝7.7Hz，1H)，7.71(d.J＝7.7 Hz，1H)，8.46(d，J＝7.7Hz，1H)，8.57(s，1H) 135-137
177 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.00(d，J＝70Hz，6H)1.44(s，9H) 2.23-2.50(m，1H)2.39(s，3H)4.11(d，J＝7.5Hz，2H)7.37(dd，J＝7.9， 5.3Hz，1H)8.51(d，J＝7.9Hz，1H)8.67(d，J＝5.3Hz，1H)9.51(s，1H)
178 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.67(m，4H)，1.17-1.36(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.24(d，7.0Hz，2H)，7.35-7.49(m，3 H)，8.23-8.35(m，2H) 106-107
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
179 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.56-0.63(m，4H)，1.22-1.29(m，1 H)，1.43(s，9H)，2.42(s，3H)，2.44(s，3H)，4.24(d，J＝6.8Hz，2H)，7.27 -7.35(m，2H)，8.06-8.13(m，2H) 132-134
180 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)，1.19-1.31(m，1 H)，1.44(s，9H)，2.43(s，3H)，2.71(s，3H)，4.19(d，J＝6.8Hz，2H)，7.18 -7.34(m，3H)，8.05-8.13(m，1H)
181 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)1.10-1.36(m，1H) 1.27(t，J＝7.5Hz，3H)1.44(s，9H)2.43(s，3H)3.12(q，J＝7.5Hz，2H) 4.17(d，J＝6.6Hz，2H)7.14-7.39(m，3H)7.93-8.01(m，1H) 120-122
182 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.25-0.69(m，4H)1.06-1.34(m，1H) 1.27(d，J＝7.0Hz，6H)1.43(s，9H)2.42(s，3H)3.86-4.09(m，1H)4.15 (d，J＝7.0Hz，2H)7.08-7.49(m，3H)7.69-7.90(m，1H) 168-169
183 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.62(m，4H)1.07-1.31(m，1H) 1.43(s，9H)2.42(s，3H)4.13(d，J＝7.0Hz，2H)7.39-7.62(m，2H)7.68 (d，J＝7.0Hz，1H)7.82(d，J＝7.0Hz，1H) 90-91
184 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.64(m，4H)1.16-1.35(m，1H) 1.45(s，9H)2.46(s，3H)4.25(d，J＝7.0Hz，2H)7.54(t，J＝7.7Hz，1H) 7.70(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.56(s，1H) 93-94
185 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.62(m，4H)，1.18-1.29(m，1 H)，1.43(s，9H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，7.04-7.22(m，2 H)，7.35-7.43(m，1H)，8.06-8.16(m，J＝7.8，1H) 182-183
186 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.59(m，4H)，1.17-1.30(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝6.8Hz，2H)，7.26-7.31(m，2 H)，7.38-7.45(m，1H)，7.92-7.96(m，1H)
187 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.18-1.34(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.23(d，J＝7.0Hz，2H)，7.30-7.46(m，2 H)，8.10-8.27(m，2H)
188 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.63(m，4H)1.16-1.35(m，1H) 1.44(s，9H)2.44(s，3H)4.22(d，J＝7.0Hz，2H)7.39(d，J＝8.9Hz，2H) 8.21(d，J＝8.9Hz，2H) 94-95
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
189 1H NMR(300MHz，CHLOROFORM-d)d ppm 0.51-0.58(m，4H)，1.16-1.28(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝7.0Hz，2H)，7.21(t，J＝7.3Hz， 1H)，7.33(t，J＝7.3Hz，1H)，7.62(d，J＝7.3Hz，1H)，7.89(d，J＝7.3Hz，1
190 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.63(m，4H)，1.17-1.34(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝7.0Hz，2H)，7.14-7.38(m，2 H)，7.58-7.66(m，1H)，7.85-7.93(m，1H)
191 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.61(m，4H)，1.15-1.33(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，7.01-7.08(m，1 H)，7.24-7.42(m，1H)，7.87-7.99(m，2H)
192 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.65(m，4H) 1.15-1.36(m，1H) 1.44(s，9H)2.45(s，3H)4.23(d，J＝7.0Hz，2H)7.16(t，J＝7.9Hz，1H) 7.73-7.81(m，1H)8.18-8.26(m，1H)8.62(t，J＝1.5Hz，1H) 114-115
193 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.62(m，4H)，1.20-1.32(m，1 H)，1.43(s，9H)，2.43(s，3H)，3.86(s，3H)，4.21(d，J＝6.8Hz，2H)，6.93 (d，J＝9.0Hz，2H)，8.24(d，J＝9.0Hz，2H)
194 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.67(m，4H)，1.17-1.34(m，1 H)，1.44(s，9H)，2.44(s，3H)，3.88(s，3H)，4.23(d，J＝7.0Hz，2H)，6.99 -7.05(m，1H)，7.30-7.37(m，1H)，7.84-7.92(m，2H) 108-109
195 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.17-1.30(m，1 H)，1.42(s，9H)，2.42(s，3H)，3.91(s，3H)，4.17(d，J＝7.0Hz，2H)，6.93 -7.01(m，2H)，7.33-7.42(m，1H)，7.96(dd，J＝7.8，1.8Hz，1H)
196 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.17-1.31(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.23(d，J＝7.0Hz，2H)，7.24-7.32(m，1 H)，7.45(t，J＝7.9Hz，1H)，8.12-8.22(m，2H) 106-108
197 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.59(m，4H)，1.11-1.33(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.18(d，J＝6.6Hz，2H)，7.28-7.49(m，3 H)，8.01-8.10(m，1H)
198 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.56-0.63(m，4H)，1.20-1.30(m，1 H)，1.44(s，9H)，2.43-2.48(m，3H)，4.24(d，J＝7.0Hz，2H)，5.94(tt， J＝53.2，3.0Hz，1H)，7.26-7.32(m，1H)，7.39-7.48(m，1H)，8.13-8.21 109-111
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
199 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.36-0.74(m，4H)1.18-1.38(M，1H) 1.45(s，9H)2.45(s，3H)4.14(d，J＝6.6Hz，2H)6.66-7.05(m，2H)7.24 -7.51(m，1H)8.10-8.19(m，1H)13.16(s，1H) 178-180
200 1H NM(300MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，4H)1.20-1.35(m，1H) 1.43(s，9H)2.42(s，3H)2.93(s，3H)4.18(d，J＝6.8Hz，2H)6.57-6.69 (m，2H)7.28-7.36(m，1H)8.34(dd，J＝7.9，1.7Hz，1H)8.53-8.70(m，1 158-159
201 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.70(m，4H)，1.17-1.35(m，1 H)，1.40(s，9H)，2.48(s，3H)，3.22(s，6H)，4.36(d，J＝7.0Hz，2H)，7.57 (t，J＝7.9Hz，1H)，8.13(d，J＝7.9Hz，1H)，8.35(d，J＝7.9Hz，1H)，8.54(s， 128-130
202 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.67(m，4H)1.14-1.31(m，1H) 1.19(t，J＝7.1Hz，6H)1.43(s，9H)2.43(s，3H)3.41(q，J＝7.1Hz，4H) 4.22(d，J＝7.0Hz，2H)6.79(dd，J＝8.2，2.8Hz，1H)7.26(t，J＝7.6Hz，1H) 7.59(d，J＝7.6Hz，1H)7.67-7.73(m，1H) 89-90
203 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)，1.20(t，J＝7.0Hz， 6H)，1.14-1.34(m，1H)，1.42(s，9H)，2.41(s，3H)，3.41(q，J＝7.0Hz，4 H)，4.19(d，J＝7.0Hz，2H)，6.66(d，J＝9.2Hz，2H)，8.15(d，J＝9.2Hz，2H) 134-136
204 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.67(m，4H)1.19-1.36(m，1H) 1.43(s，9H)1.96-2.09(m，4H)2.43(s，3H)3.29-3.41(m，4H)4.23(d， J＝7.0Hz，2H)6.67(dd，J＝8.1，2.4Hz，1H）7.27(t，J＝8.1Hz，1H)7.52- 7.57(m，1H)7.61(d，J＝7.5Hz，1H) 118-120
205 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.67(m，4H)1.19-1.36(m，1H) 1.44(s，9H)1.50-1.80(m，5H)2.45(s，3H)3.20-3.29(m，4H)4.24(d， J＝7.0Hz，2H)7.07(dd，J＝8.2，2.4Hz，1H)7.31(t，J＝8.2Hz，1H)7.77(d， J＝8.2Hz，1H)7.90-7.96(m，1H) 89-90
206 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.60(m，4H)1.15-1.33(m，1H) 1.44(s，9H)2.43(s，3H)2.99-3.12(m，4H)3.76-3.86(m，4H)4.15(d， J＝6.8Hz，2H)6.92-7.03(m，2H)7.27-7.35(m，1H)7.72(d，J＝7.6Hz，1
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
207 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.68(m，4H)1.17-1.36(m，1H) 1.44(s，9H)2.44(s，3H)3.17-3.30(m，4H)3.83-3.95(m，4H)4.23(d， J＝7.0Hz，2H)7.03(dd，J＝7.9，2.2Hz，1H)7.33(t，J＝7.9Hz，1H)7.82(d， J＝7.5Hz，1H)7.86-7.94(m，1H) 114-115
208 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.69(m，4H)1.15-1.36(m，1H) 1.43(s，9H)2.38(s，3H)2.44(s，3H)2.55-2.71(m，4H)3.21-3.39(m， 4H)4.23(d，J＝6.8Hz，2H)7.06(d，J＝7.3Hz，1H)7.32(t，J＝7.3Hz，1H) 7.79(d，J＝7.3Hz，1H)7.91(s，1H) 126-128
209 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.56-0.69(m，4H)1.14-1.38(m，1H) 1.45(s，9H)2.47(s，3H)4.28(d，J＝7.0Hz，2H)7.60(t，J＝7.5Hz，1H) 8.29(d，J＝7.5Hz，1H)8.57(d，J＝7.5Hz，1H)9.10(s，1H) 87-89
210 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.66(m，4H)1.09-1.37(m，1H) 1.45(s，9H)2.46(s，3H)4.24(d，J＝7.0Hz，2H)7.71(d，J＝8.8Hz，2H) 8.35(d，J＝8.8Hz，2H) 125-126
211 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.83(m，4H)1.09-1.38(m，1H) 1.45(s，9H)2.46(s，3H)4.25(d，J＝7.0Hz，2H)7.54(t，J＝7.7Hz，1H) 7.65-7.86(m，1H)8.43-8.59(m，2H)
212 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.80(m，4H)1.13-1.39(m，1H) 1.45(s，9H)2.46(s，3H)4.26(d，J＝6.6Hz，2H)7.53(t，J＝7.7Hz，1H) 8.03(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.63(s，1H) 76-78
213 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.64(m，4H)1.16-1.34(m，1 H)，1.44(s，9H)，2.46(s，3H)，3.94(s，3H)，4.25(d，J＝7.0Hz，2H)，8.09 (d，J＝8.8Hz，2H)，8.32(d，J＝8.8Hz，2H) 122-123
214 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.57-0.65(m，4H)，1.19-1.33(m，1 H)，1.45(s，9H)，2.46(s，3H)，4.26(d，J＝7.0Hz，2H)，8.16(d，J＝8.8Hz， 2H)，8.36(d，J＝8.8Hz，2H) 196-197
215 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.60(m，4H)1.18-1.28(m，1 H)，1.44(s，9H)，2.32(s，3H)，2.43(s，3H)，2.51(s，3H)，4.16(d，J＝7.0 Hz，2H)，7.07-7.15(m，1H)，7.16-7.21(m，1H)，7.67-7.74(m，1H) 97-98
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
216 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54(s，4H)，1.19-1.30(m，1H)， 1.43(s，9H)，2.34(s，3H)，2.42(s，3H)，2.69(s，1H)，4.18(d，J＝6.8Hz， 2H)，7.00-7.08(m，2H)，8.02-8.06(m，1H) 100-101
217 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.60(m，4H)，1.17-1.32(m，1 H)，1.43(s，9H)，2.35(s，3H)，2.43(s，3H)，2.65(s，3H)，4.19(d，J＝6.8 Hz，2H)，7.07-7.14(m，2H)，7.89(s，1H) 106-107
218 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.57(m，4H)1.07-1.32(m，1H) 1.45(s，9H)2.29(s，6H)2.43(s，3H)4.11(d，J＝6.6Hz，2H)6.95-7.18 98-100
219 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.35-0.75(m，4H)1.02-1.37(m，1H) 1.44(s，9H)2.45(s，3H)2.76(s，3H)4.20(d，J＝7.0Hz，2H)7.31(d， J＝7.9Hz，1H)7.52(d，J＝7.9Hz，1H)8.41(s，1H) 91-92
220 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.30-0.73(m，4H)0.99-1.35(m，1H) 1.45(s，9H)2.46(s，3H)4.16(d，J＝7.0Hz，2H)7.72(d，J＝8.4Hz，1H) 7.84(d，J＝8.4Hz，1H)8.15(s，1H) 159-161
221 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.67(m，4H)1.08-1.34(m，1H) 1.44(s，9H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)6.98-7.12(m，2H)7.71 -7.87(m，1H) 170-172
222 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.69(m，4H)1.08-1.36(m，1H) 1.44(s，9H)2.45(s，3H)4.21(d，J＝7.0Hz，2H)6.98-7.35(m，2H)7.76 -7.93(m，1H)
223 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.44-0.62(m，4H)1.13-1.29(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.13(d，J＝6.8Hz，2H)，6.90(t，J＝7.8Hz， 2H)，7.20-7.32(m，1H) 123-124
224 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)1.18-1.27(m，1 H)，1.43(s，9H)，2.44(s，3H)，4.20(d，J＝7.1Hz，2H)，6.79-6.93(m，2 H)，8.09-8.21(m，1H) 111-112
225 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.63(m，4H)，1.19-1.30(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.21(d，J＝7.1Hz，2H)，7.06-7.16(m，1 H)，7.40-7.50(m，1H)，7.93-8.02(m，1H)
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
226 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.16-1.29(m，1 H)，1.43(s，9H)，2.45(s，3H)，4.20(d，J＝7.0Hz，2H)，7.09-7.21(m，2 H)，8.02-8.12(m，1H) 108-110
227 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.62(m，4H)，1.15-1.30(m，1 H)，1.43(s，9H)，2.45(s，3H)，4.20(d，J＝7.1Hz，2H)，7.24-7.35(m，2 H)，8.00(t，J＝8.0Hz，1H) 121-131
228 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)，1.17-1.29(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.19(d，J＝6.8Hz，2H)，6.89-7.00(m，1 H)，7.53-7.67(m，2H) 92-94
229 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.61(m，4H)，1.18-1.28(m，1 H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝7.0Hz，2H)，6.09-7.10(m，1 H)，7.33-7.40(m，1H)7.94-8.03(m，1H) 126-128
230 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.61(m，4H)，1.17-1.28(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.20(d，J＝7.0Hz，2H)，6.93-7.04(m，1 H)，7.43-7.52(m，1H)，8.19-8.26(m，1H) 113-114
231 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.65(m，4H)，1.06-1.35(m，1) 1.44(s，9H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)6.79-6.93(m，1H)7.59 -7.74(m，1H)8.36-8.45(m，1H) 95-96
232 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.63(m，4H)，1.16-1.29(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.19(d，J＝7.0Hz，2H)，7.23-7.28(m，1 H)，7.30-7.37(m，1H)，7.90-7.95(m，1H) 129-131
233 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.30(s，1H) 1.44(s，9H)，2.46(s，3H)，4.23(d，J＝7.0Hz，2H)，7.43(t，J＝1.9Hz，1 H)，8.12(d，J＝1.9Hz，2H)
234 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.64(m，4H)，1.14-1.34(m，1H) 1.43(s，9H)2.43(s，3H)3.80(s，3H)3.87(s，3H)4.19(d，J＝6.6Hz，2 H)6.86-6.98(m，2H)7.52-7.59(m，1H) 83-85
235 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.59(m，4H)1.15-1.32(m，1H) 1.43(s，9H)2.43(s，3H)3.88(s，3H)3.95(s，1H)4.17(d，J＝6.6Hz，2 H)6.96(d，J＝7.5Hz，1H)7.07(t，J＝7.5Hz，1H)7.46(d，J＝7.5Hz，1H) 93-94
236 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.62(m，4H)1.19-1.32(m，1 H)，1.41(s，9H)，2.41(s，3H)，3.85(s，3H)，3.85(s，3H)，4.16(d，J＝7.9 Hz，2H)，6.46-6.56(m，2H)，8.06-8.14(m，1H)
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
237 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.59(m，4H)1.17-1.33(m，1H) 1.42(s，9H)1.42(t，J＝7.0Hz，3H)1.46(t，J＝7.0Hz，3H)2.40(s，3H) 4.07(q，J＝7.0Hz，2H)4.11-4.20(m，4H)6.46-6.51(m，2H)8.02-8.07 116-118
238 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.57(m，4H)1.17-1.31(m，1H) 1.39(t，J＝7.0Hz，6H)1.43(s，9H)2.42(s，3H)4.03(q，J＝7.0Hz，2H) 4.11(q，J＝7.0Hz，2H)4.17(d，J＝6.8Hz，2H)6.88-6.91(m.2H)7.47- 97-99
239 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)1.17-1.29(m，1 H)，1.43(s，9H)，2.35(s，3H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，6.92 -7.02(m，1H)，7.13-7.22(m，1H)，7.85-7.92(m，1H) 117-119
240 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)1.16-1.35(m，1H) 1.44(s，9H)2.44(s，3H)2.57(d，J＝2.2Hz，3H)4.17(d，J＝7.0Hz，2H) 6.98-7.13(m，1H)7.09-7.24(m，1H)7.79(d，J＝7.5Hz，1H) 94-96
241 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.64(m，4H)1.18-1.37(m，1H) 1.44(s，9H)2.44(s，3H)2.66(s，3H)4.19(d，J＝6.6Hz，2H)6.92-7.06 (m，1H)7.09-7.21(m，1H)7.75-7.85(m，1H) 91-93
242 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)1.19-1.30(m，1 H)，1.44(s，9H)，2.43(s，3H)，2.69(s，3H)，4.18(d，J＝6.8Hz，2H)，7.17 -7.23(m，2H)，8.06(d，J＝8.9Hz，1H) 108-109
243 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)1.11-1.34(m，1H) 1.44(s，9H)2.44(s，3H)2.65(s，3H)4.16(d，J＝6.6Hz，2H)7.14(t， J＝7.5Hz，1H)7.39(d，J＝7.5Hz，1H)7.76(d，J＝7.5Hz，1H) 88-90
244 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.54(m，4H)，1.08-1.22(m，1 H)，1.45(s，9H)，2.31(s，3H)，2.44(s，3H)，4.11(d，J＝6.8Hz，2H)，7.04 -7.24(m，3H) 159-160
245 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.69(m，4H)1.16-1.28(m，1 H)，1.44(s，9H)，2.44(s，3H)，2.67(s，3H)，4.15(d，J＝6.8Hz，2H)，7.02 -7.11(m，1H)，7.54-7.61(m，1H)，7.74-7.81(m，1H) 89-90
246 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.58(m，4H)1.18-1.30(m，1 H)，1.43(s，9H)，2.34(s，3H)，2.43(s，3H)，4.19(d，J＝7.0Hz，2H)，7.10 -7.16(m，1H)，7.44-7.48(m，1H)，7.83-7.90(m，1H) 82-84
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
247 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.59(m，4H)，1.17-1.27(m，1 H)，1.44(s，9H)，2.43(s，3H)，2.46(s，3H)，4.15(d，J＝6.8Hz，2H)，7.17 -7.27(m，2H)，7.46-7.53(m，1H) 142-144
248 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.54(m，4H)，1.10-1.23(m，1 H)，1.45(s，9H)，2.31(s，3H)，2.44(s，3H)，4.12(d，J＝6.8Hz，2H)，7.00 -7.15(m，2H)，7.34-7.41(m，1H) 89-90
249 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.59(m，4H)，1.15-1.29(m，1 H)，1.44(s，9H)，2.43(s，3H)，2.51(s，3H)，4.15(d，J＝6.8Hz，2H)，7.20 -7.29(m，2H)，7.35-7.42(m，1H) 149-151
250 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)1.11-1.33(m，1H) 1.44(s，9H)2.46(s，3H)4.21(d，J＝7.0Hz，2H)7.26(t，J＝7.0Hz，1H) 7.58-7.72(m，1H)8.20-8.34(m，1H)
251 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.67(m，4H)1.08-1.39(m，1H) 1.44(s，9H)2.46(s，3H)4.22(d，J＝7.0Hz，2H)7.20(t，J＝8.8Hz，1H) 7.56-7.72(m，1H)8.43(dd，J＝6.8，2.4Hz，1H) 113-115
252 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.17-1.31(m，1 H)，1.44(s，9H)，2.46(s，3H)，4.23(d，J＝7.0Hz，2H)，7.18-7.28(m，1 H)，8.40-8.47(m，1H)，8.57(dd，J＝7.3，1.9Hz，1H) 123-124
253 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.69(m，4H)，1.17-1.34(m，1 H)，1.45(s，9H)，2.47(s，3H)，4.24(d，J＝7.0Hz，2H)，7.36-7.43(m，1 H)，8.08-8.15(m，1H)，8.35(s，1H) 100-102
254 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.37-0.70(m，4H)0.99-1.33(m，1H) 1.44(s，9H)2.44(s，3H)4.15(d，J＝6.6Hz，2H)7.07-7.20(m，1H)7.48 -7.58(m，1H)7.64-7.75(m，1H) 110-112
255 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.33-0.78(m，4H)0.99-1.35(m，1H) 1.42(s，9H)2.42(s，3H)4.13(d，J＝7.0Hz，2H)7.08-7.57(m，2H)7.76 -8.02(m，1H)
256 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.42-0.55(m，4H)1.03-1.30(m，1H) 1.44(s，9H)2.43(s，3H)4.10(d，J＝7.0Hz，2H)7.19-7.51(m，3H) 128-130
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
257 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.64(m，4H)1.16-1.30(m，1 H)，1.45(s，9H)，2.46(s，3H)，4.19(d，J＝7.0Hz，2H)，7.49-7.57(m，2 H)，8.24-8.27(m，1H) 100-102
258 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.24-0.80(m，4H)1.04-1.34(m，1H) 1.45(s，9H)2.45(s，3H)4.15(d，J＝7.0Hz，2H)7.37(t，J＝7.9Hz，1H) 7.70(d，J＝7.9Hz，1H)7.88(d，J＝7.9Hz，1H) 93-94
259 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.68(m，4H)1.14-1.37(m，1H) 1.45(s，9H)2.46(s，3H)4.23(d，J＝7.0Hz，2H)7.51-7.59(m，1H)8.29- 8.38(m，1H)8.60-8.65(m，1H) 122-124
260 1H NMR(200MHz，CHLOROFRM-D)d ppm 0.47-0.63(m，4H)0.88(s，9H) 1.14-1.45(m，1H)，1.49(s，6H)，1.78(s，2H)，2.45(s，3H)，4.23(d， J＝7.0Hz，2H)，7.20(t，J＝9.2Hz，1H)，7.60-7.71(m，1H)，8.39-8.51(m， 88-89
261 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.62(m，4H)1.14-1.38(m，1H) 1.43(s，9H)2.42(s，3H)2.74(s，3H)3.84(s，3H)4.18(d，J＝70Hz，2 H)6.70-6.82(m，2H)8.16-8.24(m，1H) 95-96
262 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.60(m，4H)，1.18-1.29(m，1 H)，1.43(s，9H)，2.43(s，3H)，3.89(s，3H)，4.17(d，J＝6.8Hz，2H)，6.85 -6.94(m，1H)7.00-7.11(m，1H)7.63-7.71(m，1H) 87-89
263 1H NMR(300MHz，CHOROFORM-D)d ppm 0.46-0.61(m，4H)1.11-1.24(m，1 H)，1.43(s，9H)，2.42(s，3H)，3.82(s，3H)，4.11(d，J＝7.1Hz，2H)，6.66 -6.74(m，2H)，7.16-7.28(m，1H) 119-121
264 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.62(m，4H)1.13-1.33(m，1H) 1.42(s，9H)2.42(s，3H)3.90(s，3H)4.16(d，J＝7.0Hz，2H)6.89-7.01 (m，2H)7.88-7.97(m，1H) 163-165
265 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，4H)1.09-1.34(m，1H) 1.43(s，9H)2.43(s，3H)3.89(s，3H)4.17(d，J＝6.6Hz，2H)6.84-8.93 (m，1H)7.25-7.37(m，1H)7.88-7.94(m，1H) 98-100
266 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.28-0.71(m，4H)1.07-1.34(m，1H) 1.44(s，9H)2.44(s，3H)4.17(d，J＝6.6Hz，2H)6.74(t，J＝76.0Hz，1H) 7.06-7.14(m，1H)7.46-7.55(m，1H)8.14-8.19(m，1H) 169-170
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
267 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.66(m，4H)1.07-1.34(m，1H) 1.43(s，9H)2.44(s，3H)3.95(s，3H)4.18(d，J＝7.0Hz，2H)7.02(d， J＝9.2Hz，1H)7.60(d，J＝9.2Hz，1H)8.27(s，1H) 175-177
268 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)1.10-1.35(m，1H) 1.40-1.53(m，3H)1.44(s，9H)2.44(s，3H)4.11-4.30(m，2H)4.21(d， J＝7.0Hz，2H)7.00(d，J＝8.8Hz，1H)7.56(d，J＝8.8Hz，1H)8.20(s，1H) 140-142
269 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.64(m，4H)1.12-1.34(m，1H) 1.39(d，J＝6.2Hz，6H)1.43(s，9H)2.43(s，3H)4.15(d，J＝6.6Hz，2H) 4.55-4.77(m，1H)7.00(d，J＝8.8Hz，1H)7.55(d，J＝8.8Hz，1H)8.12(s， 106-108
270 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.66(m，4H)1.06-1.34(m，1H) 1.44(s，9H)2.44(s，3H)3.42(s，3H)3.76-3.86(m，2H)4.18(d，J＝6.6 Hz，2H)4.22-4.35(m，2H)7.08(d，J＝8.8Hz，1H)7.58(d，J＝8.8Hz，1H) 108-110
271 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.66(m，4H)1.13-1.34(m，1H) 1.44(s，9H)2.44(s，3H)3.41(s，3H)3.49(t，J＝5.5Hz，2H)3.65(t， J＝5.5Hz，2H)4.20(d，J＝7.0Hz，2H)6.73(d，J＝8.8Hz，1H)7.47(d，J＝8.8 Hz，1H)8.61(s，1H)9.09-9.27(m，1H) 131-132
272 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.65(m，4H)1.16-1.36(m，1H) 1.44(s，9H)2.44(s，3H)3.49(t，J＝5.5Hz，2H)3.88(t，J＝5.5Hz，2H) 4.21(d，J＝6.6Hz，2H)6.77(d，J＝8.8Hz，1H)7.42-7.53(m，1H)8.64(s， 131-133
273 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.66(m，4H)1.13-1.34(m，1H) 1.44(s，9H)2.44(s，3H)3.41(s，3H)3.49(t，J＝5.5Hz，2H)3.65(t， J＝5.5Hz，2H)4.20(d，7.0Hz，2H)6.73(d，J＝8.8Hz，1H)7.47(d，J＝8.8 Hz，1H)8.61(s，1H)9.09-9.27(m，1H) 131-132
274 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.64(m，4H)1.12(t，J＝7.2Hz，3 H)1.18-1.37(m，1H)1.43(s，9H)2.44(s，3H)2.87(s，3H)3.29(q， J＝7.2Hz，2H)4.15(d，J＝7.0Hz，2H)6.90(d，J＝8.4Hz，1H)7.43(d，J＝8.4 Hz，1H)7.92(s，1H) 101-103
275 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.66(m，4H)1.08-1.33(m，1H) 1.43(s，9H)2.29(qn，J＝7.5Hz，2H)2.43(s，3H)3.96(t，J＝7.5Hz，4H) 4.16(d，J＝6.6Hz，2H)6.48(d，J＝9.2Hz，1H)7.43(d，J＝9.2Hz，1H)7.98 100-102
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
276 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)1.09(t，J＝70Hz，6 H)1.15-1.33(m，1H)1.44(s，9H)2.43(s，3H)3.27(q，J＝7.0Hz，4H) 4.14(d，J＝7.0Hz，2H)6.94(d，J＝8.4Hz，1H)7.43(d，J＝8.4Hz，1H)7.89 131-133
277 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)1.11-1.31(m，1H) 1.44(s，9H)2.44(s，3H)2.91(s，6H)4.16(d，J＝7.0Hz，2H)6.90(d， J＝8.8Hz，1H)7.45(dd，J＝8.8，2.0Hz，1H)8.00(d，J＝2.0Hz，1H) 126-128
278 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)，1.10-1.32(m，1 H)，1.43(s，9H)，1.83-1.97(m，4H)，2.43(s，3H)，3.22-3.38(m，4H)， 4.15(d，J＝6.6Hz，2H)，6.75(d，J＝8.8Hz，1H)，7.41(dd，J＝8.8，2.6Hz，1 H)，7.91(d，J＝2.6Hz，1H)
279 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)，1.15-1.34(m，1 H)，1.44(s，5H)，1.49-1.73(m，6H)，2.43(s，3H)，3.07-3.19(m，4H) 4.15(d，J＝7.0Hz，2H)，6.97(d，J＝8.8Hz，1H)，7.45(dd，J＝8.8，2.2Hz，1 H)，7.96(d，J＝2.2Hz，1H) 138-140
280 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.65(m，4H)，1.09-1.35(m，1H) 1.45(s，9H)2.44(s，3H)3.05-3.22(m，4H)3.75-3.91(m，4H)4.16(d， J＝6.6Hz，2H)6.98(d，J＝8.8Hz，1H)7.51(dd，J＝8.8，1.8Hz，1H)8.03(d， 86-87
281 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.43-0.88(m，4H)，1.08-1.39(m，1H) 1.45(s，9H)2.46(s，3H)4.23(d，J＝7.0Hz，2H)7.03-7.55(m，1H)8.27 -8.77(m，2H) 195-197
282 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)，1.16-1.31(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.21(d，J＝7.0Hz，2H)，6.93-7.03(m，1 H)，7.83-7.93(m，1H) 82-84
283 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.60(m，4H)，1.17-1.29(m，1 H)，1.43(s，9H)，2.45(s，3H)，4.20(d，J＝7.0Hz，2H)，6.88-7.01(m，1 H)7.94-8.03(m，1H) 78-79
284 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.63(m，4H)，1.16-1.30(m，1 H)，1.44(s，9H)，2.45(s，3H)，4.18(d，J＝7.0Hz，2H)，7.20-7.29(m，1 H)，7.83-7.94(m，2H) 112-114
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
285 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.67(m，4H)1.08-1.35(m，1H) 1.44(s，9H)2.45(s，3H)4.21(d，J＝7.0Hz，2H)6.93-7.07(m，1H)7.94 -8.12(m，1H) 76-77
286 1H NMR(300MHz，CHLOROFORM-D)d pmm 0.52-0.60(m，4H)，1.18-1.34(m，1 H)，1.43(s，9H)，2.42(s，3H)，3.89(s，3H)，3.90(s，3H)，3.99(s，3H)， 4.18(d，J＝6.8Hz，2H)，6.71(d，J＝8.9Hz，1H)，7.78(d，J＝8.9Hz，1H) 88-89
287 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.63(m，4H)，1.17-1.28(m，1 H)，1.43(s，9H)，2.33(d，J＝2.0Hz，3H)，2.44(s，3H)，4.21(d，J＝7.0Hz， 2H)，6.91-6.99(m，1H)，7.71-7.81(m，1H) 122-124
288 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.42-0.69(m，4H)0.94-1.34(m，1H) 1.45(s，9H)2.45(s，3H)4.12(d，J＝7.0Hz，2H)6.92-7.05(m，1H)7.40 -7.68(m，1H) 109-111
289 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.37-0.58(m，4H)1.06-1.26(m，1H) 1.45(s，9H)2.44(s，3H)4.09(d，J＝7.0Hz，2H)7.34-7.52(m，2H) 182-183
290 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.67(m，4H)，1.15-1.32(m，1 H)，1.45(s，9H)，2.45(s，3H)，4.28(d，J＝7.0Hz，2H)，7.28-7.39(m，1 H)，7.72-7.84(m，1H)，8.30(d，J＝7.7Hz，1H)，8.75(d，J＝7.7Hz，1H)
291 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.59(d，J＝6.6Hz，4H)，1.17-1.38(m， 1H)，1.45(s，9H)，2.46(s，3H)，4.24(d，J＝7.0Hz，2H)，7.30-7.43(m，1 H)，8.43-8.55(m，1H)，8.63-8.71(m，1H)，9.46-9.52(m，1H)
292 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.64(m，4H)，1.18-1.31(m，1 H)，1.46(s，9H)，2.47(s，3H)，4.26(d，J＝7.0Hz，2H)，8.58-8.64(m，1 H)，8.68-8.74(m，1H)，9.49-9.54(m，1H)
293 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.56(m，4H)，1.10-1.28(m，1 H)，1.44(s，9H)，2.43(s，3H)，2.54(s，3H)，4.19(d，J＝6.8Hz，2H)，7.16 -7.22(m，1H)，7.51-7.55(m，1H)，8.46-8.51(m，1H) 88-89
294 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.64(d，4H)，1.08-1.38(m，1 H)，1.44(s，9H)，2.42(s，3H)，2.46(s，3H)，4.24(d，J＝7.0Hz，2H)，7.31 -7.47(m，1H)，7.67-7.94(m，1H)，8.35-8.50(m，1H)
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
295 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.42-0.66(m，4H)，1.14-1.34(m，1 H)，1.44(s，9H)，2.45(s，3H)，2.97(s，3H)，4.18(d，J＝6.6Hz，2H)，7.24 -7.46(m，1H)，7.64-7.93(m，1H)，8.41-8.55(m，1H)
296 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.62(m，4H)1.16-1.31(m，1H) 1.44(s，9H) 2.45(s，3H)2.62(s，3H)4.22(d，J＝7.0Hz，2H)7.22(d， J＝7.9Hz，1H) 8.38(dd，J＝7.9，2.2Hz，1H)9.38(d，J＝2.2Hz，1H) 228-230
297 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.67(m，4H)，1.15-1.33(m，1 H)，1.29(t，J＝7.6Hz，3H)，1.44(s，9H)，2.45(s，3H)，2.73(d，J＝7.6Hz， 2H)，4.29(d，J＝7.0Hz，2H)，7.18(d，J＝5.0Hz，1H)，8.15(s，1H)，8.62 104-106
298 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.43-0.62(m，4H)1.05-1.35(m，1H) 1.45(s，9H)2.45(s，3H)4.16(d，J＝7.0Hz，2H)7.58(d，J＝4.8Hz，1H) 8.77(d，J＝4.8Hz，1H)9.20(s，1H) 74-76
299 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.40-0.58(m，4H)，1.07-1.29(m，1 H)，1.46(s，9H)，2.29(s，3H)，2.45(s，3H)，2.52(s，3H)，4.11(d，J＝6.8 Hz，2H)，6.96(d，J＝5.1Hz，1H)，8.31(d，J＝5.1Hz，1H) 156-157
300 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.66(m，4H)，1.09-1.38(m，1 H)，1.44(s，9H)，2.46(s，3H)，4.24(d，J＝22.0Hz，2H)，7.20-7.34(m，1 H)，8.21-8.32(m，1H)，8.45-8.59(m，1H) 83-84
301 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)1.10-1.34(m，1H) 1.45(s，9H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)7.28(dd，J＝7.5，4.8Hz，1 H)8.25(dd，J＝7.5，2.2Hz，1H)8.41(dd，J＝4.8，2.2Hz，1H) 124-125
302 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.65(m，4H)1.14-1.35(m，1H) 1.44(s，H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)7.36(d，J＝5.3Hz，1H) 8.47(d，J＝5.3Hz，1H)9.21(s，1H)
303 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.67(m，4H)1.13-1.37(m，1H) 1.45(s，9H)2.46(s，3H)4.23(d，J＝6.6Hz，2H) 8.60(dd，J＝2.6，1.3Hz，1 H)8.73(d，J＝2.6Hz，1H)9.36(d，J＝1.3Hz，1H) 152-154
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
304 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.58(m，4H)1.08-1.34(m，1H) 1.45(s，9H)2.44(s，3H)4.19(d，J＝7.0Hz，2H)7.17(dd，J＝7.9，4.8Hz，1 H)7.93(d，J＝7.9Hz，1H)8.58(d，J＝4.8Hz，1H) 141-142
305 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.61(m，4H)1.09-1.34(m，1H) 1.45(s，9H)2.46(s，3H)4.17(d，J＝7.0Hz，2H)8.37(d，J＝2.6Hz，1H) 8.52(d，J＝2.6Hz，1H) 115-116
306 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.61(m，4H)1.06-1.31(m，1H) 1.44(s，9H)2.44(s，3H)4.15(d，J＝7.0Hz，2H)7.26(d，J＝8.4Hz，1H) 7.67(d，J＝8.4Hz，1H) 143-145
307 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.44-0.66(m，4H)1.07-1.37(m，1H) 1.45(s，9H)2.47(s，3H)4.19(d，J＝7.0Hz，2H)7.77(s，1H)8.41(s，1 110-112
308 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.40-0.64(m，4H)0.98-1.32(m，1H) 1.46(s，9H)2.46(s，3H)4.11(d，J＝7.0Hz，2H)8.48(s，2H) 260-261
309 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.64(m，4H)，1.17-1.29(m，1 H)，1.45(s，9H)，2.47(s，3H)，4.20(d，J＝6.8Hz，2H)，8.23(d，J＝2.6Hz， 1H)，8.36(d，J＝2.6Hz，1H) 113-134
310 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)1.15-1.34(m，1H) 1.43(s，9H)1.44(t，J＝7.0Hz，3H)2.43(s，3H)4.18(d，J＝7.0Hz，2H) 4.53(q，J＝7.0Hz，2H)6.90(dd，J＝7.5，4.8Hz，1H)8.19(dd，J＝4.8，2.2Hz， 1H)8.28(dd，J＝7.5，2.2Hz，1H) 102-104
311 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.60(m，4H)，1.22-1.35(m，1 H)，1.40(d，J＝6.2Hz，6H)，1.43(s，9H)，2.42(s，3H)，4.17(d，J＝7.0Hz， 2H)，5.35-5.55(m，1H)，6.80-6.92(m，1H)，8.13-8.26 (m，2H) 151-153
312 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.20-1.31(m，1 H)，1.43(s，9H)，2.45(s，3H)，2.52(s，3H)，4.29(d，J＝6.8Hz，2H)，7.01 -7.10(m，1H)，8.46-8.53(m，2H) 138-139
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
313 1H NMR(200MHz，CHLOROFORM-D)d ppm 5.11-5.22(m，4H)5.82-6.07(m，1H) 6.16(s，9H)7.15(s，3H)8.85(d，J＝7.0Hz，2H)11.79(dd，J＝7.5，4.8Hz， 1H)11.83-11.96(m，3H)12.04-12.19(m，2H)12.92(dd，J＝4.8，2.2Hz，1 H)13.14(dd，J＝7.5，2.2Hz，1H) 111-114
314 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.66(m，4H)1.07-1.33(m，1H) 1.43(s，9H)2.45(s，3H)4.08(s，3H)4.14(s，3H)4.16(d，J＝6.6Hz，2 H)7.39(s，1H) 124-126
315 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)，1.14-1.31(m，1 H)，1.43(s，9H)，1.82-1.94(m，4H)，2.43(s，3H)，3.38-3.51(m，4H)， 4.13(d，J＝6.6Hz，2H)，6.58(dd，J＝7.5，4.8Hz，1H)，7.89(dd，J＝7.5，2.2 Hz，1H)，8.17(dd，J＝4.8，2.2Hz，2H) 97-98
316 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.34-0.78(m，4H)1.03-1.38(m，1H) 1.44(s，9H)2.45(s，3H)2.89(s，3H)4.18(d，J＝7.0Hz，2H)6.73-6.81 (m，1H)8.45-8.57(m，1H) 67-69
317 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.66(m，4H)，1.12-1.34(m，1 H)，1.44(s，9H)，2.46(s，3H)，3.98(s，3H)，4.22(d，J＝7.0Hz，2H)，7.43 (d，J＝0.9Hz，1H)，7.65(d，J＝0.9Hz，1H) 127-128
318 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.60(m，4H)，0.85(t，J＝7.3Hz， 3H)，1.20-1.31(m，1H)，1.43(s，9H)，1.52-1.70(m，2H)，2.42(s，3 H)，3.07-3.16(m，2H)，4.17(d，J＝6.8Hz，2H)，7.39-7.54(m，5H)，8.18 104-105
319 1H MHR(200MHz，CHLOROFORM-D)d ppm 0.54-0.70(m，4H)1.07-1.31(m，1H) 1.44(s，9H)2.47(s，3H)4.21(d，J＝7.0Hz，2H)7.19(d，J＝4.0Hz，1H) 7.33(d，J＝4.0Hz，1H) 129-130
320 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.68(m，4H)1.16-1.39(m，1H) 1.46(s，9H)2.48(s，3H)4.27(d，J＝7.0Hz，2H)7.84(d，J＝9.7Hz，1H) 8.33(d，J＝9.7Hz，1H)8.77(s，1H) 139-141
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
321 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.71(m，4H)1.17-1.40(m，1H) 1.47(s，9H)2.47(s，3H)4.25(d，J＝7.0Hz，2H)7.65(dd，J＝8.1，7.3Hz，1 H)8.05(d，J＝8.1Hz，1H)8.56(d，J＝6.2Hz，1H)8.62(dd，J＝7.3，1.5Hz，1 H)9.14(d，J＝6.2Hz，1H)9.26(s，1H) 109-110
322 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.67(m，4H)1.03-1.38(m，1H) 1.45(s，9H)2.44(s，3H)4.15(d，J＝7.0Hz，2H)7.38(dd，J＝8.1，4.2Hz，1 H)7.56(dd，J＝8.1，7.0Hz，1H)7.84(dd，J＝8.1，1.8Hz，1H)8.06(dd， J＝7.0，1.8Hz，1H)8.15(dd，J＝8.1，2.0Hz，1H)9.04(dd，J＝4.2，2.0Hz，1 193-195
323 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.68(m，4H)1.12-1.39(m，1H) 1.47(s，9H)2.48(s，3H)4.23(d，J＝7.0Hz，2H)7.57(ddd，J＝8.4，6.8，1.5 Hz，1H)7.71(ddd，J＝8.4，6.8，1.5Hz，1H)8.01(d，J＝4.4Hz，1H)8.13(d， J＝7.5Hz，1H)9.00(d，J＝4.4Hz，1H)9.05(dd，J＝7.5，1.1Hz，1H) 124-126
324 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.54(m，4H)，1.12-1.24(m，1 H)，1.48(s，9H)，2.46(s，3H)，4.22(d，J＝7.9Hz，2H)，7.52-7.87(m，4 H)，8.56-8.72(m，2H)
325 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.43-0.75(m，4H)，1.15-1.41(m，1 H)，1.50(s，9H)，2.54(s，3H)，4.13-4.50(m，2H)，8.02-8.27(m，2H)， 8.72-8.92(m，1H)，9.54-9.75(m，1H)，9.90-10.21(m，1H) 140-141
326 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.72(m，4H)1.12-1.38(m，1H) 1.48(s，9H)2.49(s，3H)4.23(d，J＝7.0Hz，2H)7.57(t，J＝8.4Hz，1H) 7.72(t，J＝8.4Hz，1H)7.98(s，1H)8.04(d，J＝8.4Hz，1H)9.00(d，J＝8.4 201-203
327 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.59(m，4H)1.01-1.28(m，1H) 1.46(s，9H)2.44(s，3H)4.10(d，J＝7.0Hz，2H)7.56(d，J＝9.2Hz，1H) 7.65(d，J＝9.2Hz，1H)8.09(d，J＝2.6Hz，1H)8.80(d，J＝2.6Hz，1H) 172-174
328 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.36-0.65(m，4H)1.06-1.36(m，1H) 1.46(s，9H)2.46(s，3H)4.18(d，J＝7.0Hz，2H)7.69(d，J＝5.3Hz，1H) 7.92(d，J＝5.3Hz，1H)8.69(s，1H) 147-149
329 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(s，9H)2.07(s，3H)3.15(t， J＝7.0Hz，2H)4.46(t，J＝7.0Hz，2H)7.10-7.19(m，2H)7.22-7.36(m，3 H)7.40(dd，J＝7.9，4.8Hz，1H)8.56(d，J＝7.9Hz，1H)8.69(d，J＝4.8Hz，1
330 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.45-0.61(m，4H)1.02-1.22(m，1H) 1.24(s，9H)1.39(s，9H)2.39(s，3H)4.10(d，J＝7.0Hz，2H) 102-104
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
331 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.60(m，4H)，1.09-1.20(m，1 H)，1.39(s，9H)，1.83-2.02(m，2H)，2.12-2.42(m，4H)，2.39(s，1H)， 3.22-3.35(m，1H)，4.08(d，J＝6.8Hz，2H) 189-191
332 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.65(m，4H)1.02-2.07(m，12 H)1.39(s，9H)2.38(s，3H)4.08(d，J＝7.0Hz，2H) 141-142
333 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.64(m，4H)，1.07-1.36(m，1 H)，1.44(s，9H)，2.47(s，3H)，4.15(d，J＝7.0Hz，2H)
334 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)1.05-1.29(m，1H) 1.43(s，9H)2.46(s，3H)4.14(d，J＝7.0Hz，2H)6.21(tt，J＝53.2，5.7Hz， 93-94
335 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.60(m，4H)，1.08-1.22(m，1 H)，1.41(s，9H)，2.41(s，3H)，2.47-2.64(m，2H)，2.68-2.76(m，2H)， 4.08(m，J＝6.8Hz，2H) 102-103
336 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.59(m，4H)，1.08-1.20(m，1 H)，1.43(s，9H)，2.47(s，3H)，4.15(d，J＝7.0Hz，2H) 147-148
337 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.59(m，4H)1.05-1.36(m，2H) 1.37(s，9H)1.60-1.74(m，1H)2.07-2.20(m，1H)2.38(s，3H)2.49- 2.65(m，1H)4.07(d，J＝6.6Hz，2H)7.08-7.32(m，5H) 110-112
338 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.44(s，3H)，3.29(s，3 H)，3.70(t，J＝5.2Hz，2H)，4.34(t，J＝5.1Hz，2H) 69-71
339 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.35-0.51(m，4H)，1.01-1.16(m，1 H)，1.37(s，9H)，2.36(s，3H)，3.76(s，2H)，4.01(d，J＝7.0Hz，2H)，7.14 -7.22(m，1H)，7.22-7.38(m，4H) 92-94
340 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.43-0.54(m，4H)，1.04-1.18(m，1 H)，1.38(s，9H)，2.38(s，3H)，3.97(s，2H)，4.07(d，J＝7.0Hz，2H)，6.91 -6.94(m，2H)，7.13-7.17(m，1H) 157-159
341 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.21-0.54(m，4H)，0.87-1.08(m，1 H)，1.36(s，9H)，2.22(s，3H)，2.35(s，3H)，3.92(dd，J＝14.2，6.5Hz，1 H)，4.08(dd，J＝14.2，7.5Hz，1H)，6.14(s，1H)，7.23-7.36(m，3H)，7.50 147-148
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
342 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.32-0.47(m，4H)，0.99-1.10(m，1 H)，1.37(s，9H)，2.36(s，3H)，3.75(s，6H)，3.78(s，2H)，3.96(d，J＝7.0 Hz，2H)，6.69-6.88(m，3H) 89-91
343 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.37(s，3H)，4.92- 5.00(m，2H)，5.02-5.30(m，2H)，5.89-6.11(m，1H)，7.35-7.47(m，3 H)，8.26-8.35(m，2H)
344 1H NMR(200MHz，CHLOROFFORM-D)d ppm 1.44(s，9H)2.44(s，3H)3.34(m，2H) 3.81(t，J＝5.5Hz，2H)4.44(t，J＝5.5Hz，2H)7.54(t，J＝7.5Hz，3H)7.71 (d，J＝7.5Hz，1H)8.45(d，J＝7.5Hz，1H)8.56(s，1H) 172-173
345 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.44(s，3H)，3.34(s，3 H)，3.81(t，J＝5.4Hz，2H)，4.42(t，J＝5.4Hz，2H)，7.26-7.33(m，1H)， 7.55-7.61(m，1H)，8.18-8.23(m，1H)，8.40-8.44(m，1H) 89-91
346 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.43(s，3H)3.34(s，3H) 3.80(t，J＝5.5Hz，2H)4.41(t，J＝5.5Hz，2H)7.16(t，J＝7.9Hz，1H)7.78 (d，J＝7.9Hz，1H)8.23(d，J＝7.9Hz，1H)8.62(s，1H) 119-121
347 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.42(s，3H)，3.31(s，3 H)，3.77(t，J＝5.5Hz，2H)，4.37(t，J＝5.5Hz，2H)，7.07-7.21(m，2H)， 8.02-8.14(m，1H) 68-69
348 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.43(s，3H)，3.32(s，3 H)，3.78(t，J＝5.3Hz，2H)，4.38(t，J＝5.3Hz，2H)，6.92-7.04(m，1H)， 7.43-7.53(m，1H)，8.18-8.26(m，1H) 95-97
349 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.44(s，3H)3.31(s，3H) 3.75(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz，2H)7.43-7.51(m，1H)7.78- 161-163
350 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.43(s，3H)3.34(s，3H) 3.80(t，J＝5.5Hz，2H)4.42(t，J＝5.5Hz，2H)5.39-6.34(m，1H)7.18- 7.36(m，1H)7.38-7.50(m，1H)8.01-8.32(m，2H) 114-116
351 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.43(s，3H)2.66(s，3H) 3.32(s，3H)3.77(t，J＝5.5Hz，2H)4.37(t，J＝5.5Hz，2H)6.91-7.07(m， 1H)7.08-7.23(m，1H)7.72-7.90(m，1H) 106-107
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
352 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.14(t，J＝7.0Hz，3H)1.43(s，9H) 2.46(s，3H)3.47(d，J＝7.0Hz，2H)3.84(t，J＝5.5Hz，2H)4.44(t，J＝5.5 Hz，2H)7.54(t，J＝7.7Hz，1H)7.71(d，J＝7.7Hz，1H)8.46(d，J＝7.7Hz，1 91-92
353 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.42(s，3H)3.93(s，1H) 4.08(t，J＝5.3Hz，2H)4.48(t，J＝5.3Hz，2H)7.55(t，J＝7.9Hz，1H)7.72 (d，J＝7.9Hz，1H)8.42(d，J＝7.9Hz，1H)8.51(s，1H) 147-149
354 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)2.45(s，3H)3.19(t， J＝6.4Hz，2H)4.37(t，J＝6.4Hz，2H)7.55(t，J＝7.7Hz，1H)7.71(d，J＝7.7 Hz，1H)8.46(d，J＝7.7Hz，1H)8.56(s，1H) 76-78
355 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)2.16-2.33(m，2H)3.82- 3.93(m，2H)4.32-4.44(m，2H)7.37-7.50(m，1H)7.63-7.77(m，3H) 7.79-7.88(m，2H)8.35-8.44(m，1H)8.51-8.55(m，1H) 129-130
356 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.71(m，4H)1.16-1.45(m，1H) 1.37(t，J＝7.0Hz，3H)2.79(s，3H)4.34(q，J＝7.0Hz，2H)4.30(d，J＝7.9 Hz，2H)7.58(t，J＝7.7Hz，1H)7.75(d，J＝7.7Hz，1H)8.45(d，J＝7.7Hz，1 115-116
357 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.63-1.01(m，4H)1.16-1.41(m，1H) 2.34-2.73(m，3H)3.53-3.87(m，2H)7.01-7.24(m，1H)7.30-7.59(m， 1H)7.91-8.29(m，2H) 291-293
358 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.71(m，4H)1.17-1.43(m，1H) 1.25(d，J＝6.6Hz，6H)2.78(s，3H)4.10-4.35(m，1H)4.29(d，J＝7.0Hz， 2H)5.47-5.65(m，1H)7.58(t，J＝7.7Hz，1H)7.76(d，J＝7.7Hz，1H)8.44 (d，J＝7.7Hz，1H)8.55(s，1H) 212-214
359 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.70(m，4H)1.17-1.45(m，1H) 2.49(s，3H)3.13(s，6H)4.25(d，J＝7.0Hz，2H)7.57(t，J＝7.7Hz，1H) 7.74(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.56(s，1H) 138-140
360 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.71(m，4H)1.19-1.45(m，1H) 1.89-2.06(m，4H)2.59(s，3H)3.53-3.74(m，4H)4.27(d，J＝7.0Hz，2 H)7.57(t，J＝7.7Hz，1H)7.74(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H) 125-127
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
361 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.71(m，4H)1.14-1.46(m，1H) 2.43-2.57(m，4H)2.58(t，J＝6.2Hz，2H)2.78(s，3H)3.51(q，J＝6.2Hz， 2H)3.67-3.83(m，4H)4.30(d，J＝7.0Hz，2H)6.31-6.49(m，1H)7.59 (t，J＝7.7Hz，1H)7.76(d，J＝7.7Hz，1H)8.45(d，J＝7.7Hz，1H)8.55(s，1 156-158
362 1H NMR(200MHz，CHLOROFORM-d)d ppm 1.35(6H，d，J＝5.27Hz)，3.47-3.72(1 H，m)，3.67(3H，s)，7.84-7.95(1H，m)，8.52-8.61(1H，m)，8.79-8.86 (1H，m)，9.49-9.58(1H，m)
363 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，2H)，0.81-0.96(m，2 H)，1.21-1.51(m，1H)，1.36(d，J＝7.0Hz，6H)，3.45-3.67(m，1H)，4.41 (d，J＝7.5Hz，2H)，8.25(s，1H)，9.18(s，1H)，9.43(s，1H) 139-141
364 1H NMR(300MHz，CHLOROFORM-D)d ppm 1.42(t，J＝7.1Hz，3H)，2.36(s，3H) 4.33(q，J＝7.0Hz，2H)，7.24-7.33(m，1H)，7.66-7.74(m，1H)，8.27- 158-160
365 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.67(m，4H)1.20-1.38(m，1 H)2.39(s，3H)4.21(d，J＝7.0Hz，2H)7.29(t，J＝7.7Hz，1H)7.70(t， J＝7.7Hz，1H) 8.29(t，J＝7.7Hz，1H) 130-132
366 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.13-0.48(m，4H)，0.98-1.18(m，1 H)，2.15(s，3H)，4.07(d，J＝7.0Hz，2H)，7.27-7.41(m，2H)，7.47-7.63 (m，4H)，7.72(d，J＝7.5Hz，1H)，8.48(d，J＝7.5Hz，1H)，8.59(s，1H) 161-162
367 1H NMR(200MHz，CHLOROFORM-D)d ppm 2.04(s，3H)，2.22(s，3H)，2.65(s，3 H)，4.39-4.47(m，2H)，5.10-5.30(m，2H)，5.79-6.01(m，1H)，7.11- 7.33(m，3H)，7.96-8.05(m，1H)
368 1H NMR(200MHz，CHLOROFORM-D)d ppm 4.66-4.83(m，2H)，4.89-5.26(m，2 H)，5.86-6.07(m，1H)，7.10-7.56(m，13H)，8.31-8.42(m，2H) 141-143
369 1H NMR(600MHz，CHLOROFORM-d)d ppm 0.43-0.48(m，2H)0.56-0.61(m，2 H)1.13-1.20(m，1H)1.26(d，J＝7.3Hz，6H)2.13(s，3H)2.90-2.96(m， 1H)3.70(d，J＝7.3Hz，2H)7.21-7.25(m，1H)7.61-7.65(m，1H)8.17-
370 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.68(m，4H)1.14-1.36(m，1H) 1.31(d，J＝7.0Hz，6H)2.14(s，3H)2.86-3.05(m，1H)3.74(d，J＝7.0Hz， 2H)7.44-7.57(m，1H)7.64-7.73(m，1H)8.37-8.44(m，1H)8.47- 65-67
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
371 1H NMR(300MHz，CHLOROFORM-d)d ppm 0.43-0.64(m，4H)1.08-1.24(m，1H) 1.29(d，J＝7.0Hz，6H)2.14(s，3H)2.86-3.00(m，1H)3.71(d，J＝7.1Hz， 2H)7.10-7.22(m，1H)7.57-7.68(m，1H)8.30-8.39(m，1H) 76-78
372 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.65(m，4H)1.09-1.31(m，1 H)1.20(d，J＝7.0Hz，6H)2.11(s，3H)2.80-2.97(m，1H)3.68(d，J＝7.0 Hz，2H)3.90(s，3H)6.93-7.01(m，1H)7.53-7.61(m，1H)8.03-8.07 118-120
373 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)1.35-1.54(m，1H) 2.75(s，3H)4.42(d，J＝7.0Hz，2H)7.20-7.54(m，6H)7.70(d，J＝7.0Hz， 1H)8.21(d，J＝7.9Hz，1H) 115-117
374 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.74(m，4H)，1.33-1.55(m，1 H)，3.03(s，6H)，4.45(d，J＝7.0Hz，2H)，6.86-6.97(m，1H)，7.25-7.51 (m，4H)，7.67-7.80(m，3H) 156-158
375 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.66(m，4H)，1.34-1.53(m，1 H)，2.98(s，3H)，4.43(d，J＝7.5Hz，2H)，7.18-7.57(m，4H)，7.73(d， J＝7.0Hz，1H)，8.42-8.51(m，1H)，8.54-8.62(m，1H) 181-183
376 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.65(m，4H)1.34-1.52(m，1H) 2.36(s，3H)2.41(s，3H)2.74(s，3H)4.38(d，J＝7.0Hz，2H)7.17-7.42 (m，3H)7.19(s，1H)7.45(s，1H)8.19(d，J＝7.9Hz，1H) 160-161
377 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.65(m，4H)，1.32-1.50(m，1 H)，2.74(s，3H)，4.39(d，J＝7.0Hz，2H)，7.12-7.46(m，6H)，8.17-8.25 143-145
378 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.59(m，2H)，0.62-0.72(m，2 H)，1.45-1.61(m，1H)，2.75(s，3H)，4.98(d，J＝7.1Hz，2H)，7.17-7.48 (m，5H)，7.60(d，J＝7.6Hz，1H)，8.22(d，J＝7.8Hz，1H) 146-148
379 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.69(m，4H)，1.19-1.35(m，1 H)，2.74(s，3H)，2.86(s，3H)，4.78(d，J＝6.5Hz，2H)，7.15-7.40(m，5 H)，7.51-7.59(m，1H)，8.19(d，J＝6.2Hz，1H) 133-134
380 1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)，1.40-1.52(m，1 H)，2.74(s，3H)，4.57(d，J＝8.5Hz，2H)，6.92-7.03(m，1H)，7.19-7.43 (m，4H)，8.22(d，J＝7.5Hz，1H) 146-148
Table 9 (continuing)
Compound N o. H-NMR Fusing point (℃)
381 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.65(m，4H)1.18-1.42(m，1H) 1.79-2.04(m，4H)2.56-2.70(m，4H)4.15(d，J＝7.0Hz，2H)7.55(t， J＝7.7Hz，1H)7.71(d，J＝7.7Hz，1H)8.46(d，J＝7.7Hz，1H)8.57(s，1H) 159-160
382 1H NMR(200MHz，CHLOROFORM-d)d ppm 0.56-0.69(m，4H)1.28-1.50(m，1H) 4.42(d，J＝7.5Hz，2H)7.24-7.47(m，2H)7.62-7.82(m，2H)8.29-8.42 (m，1H)8.49-8.57(m，1H) 156-158
Table 10
Compound N o. Fusing point (℃) or NMR
383 178.5-180.5
384 141.5-142.5
385 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.35(s，9H)，2.25(s，3H)，3.43(s，3H)，7.38- 7.52(m，3H)，7.94-8.02(m，2H)
386 173-174.5
387 190-192
388 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.29-0.51(m，4H)，0.89-1.12(m，1H)，1.36(s， 9H)，2.29(s，3H)，3.84(d，J＝7.0Hz，2H)，7.37-7.54(m，3H)，7.91-8.01(m，2H)
389 198-199.5
390 121-124
391 122-123
392 125-127
393 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.29-0.54(m，4H)，0.99-1.19(m，1H)，1.36(s， 9H)，2.31(s，3H)，3.85(d，J＝6.6Hz，2H)，7.29-7.50(m，3H)，8.15-8.26(m，1H)
394 126-128
395 159-160
396 140.5-141.5
397 132-134
398 100-102
399 104-105
400 130-131
Table 10 (continuing)
Compound N o. Fusing point (℃) or NMR
401 149-151
402 132-135
403 110-112
404 150-152
405 69-72
406 127-129
407 124-126
408 126.5-128
409 136-138
410 136-138
411 129-131
412 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.31-0.53(m，4H)，0.94-1.11(m，1H)，1.36(s， 9H)，2.30(s，3H)，3.84(d，J＝7.0Hz，2H)，7.11-7.23(m，1H)，7.31-7.44(m，2H)， 7.87-7.95(m，2H)
413 132.5-134
414 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.29-0.58(m，4H)，0.96-1.13(m，1H)，1.36(s， 9H)，2.30(s，3H)，2.67(s，3H)，7.00-7.12(m，1H)，7.16-7.27(m，1H)，7.74-7.84
415
416
417 124-125.5
Table 10 (continuing)
Compound N o. Fusing point (℃) or NMR
418 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.30-0.44(m，4H)，0.90-1.11(m，1H)，1.38(s， 9H)，2.37(s，3H)，3.80(s，3H)，3.84(d，J＝7.0Hz，2H)，6.70-6.84(m，2H)，7.87-
419 158-160
420 97-99
421 86-88
422 145.5-147
423 146-147.5
424 85-87
425 145-146
426 156-158.5
427 207.5-208.5
428 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.35(s，9H)，2.15(s，3H)，5.21(s，2H)，7.10- 7.18(m，1H)，7.23-7.57(m，6H)，7.84-7.92(m，2H)
429 94-95
430 186.5-188
431 273-274.5
432 139-142
433 171-173
434 1H NMR(200MHz，CHLOROFORM-D)d ppm 1.20(t，J＝7.3Hz，3H)，1.36(s，9H)，2.18(s，3 H)，4.13(q，J＝7.0Hz，2H)，4.68(s，2H)，7.36-7.53(m，3H)，7.88-7.95(m，2H)
435 163.5-165
Table 10 (continuing)
Compound N o. Fusing point (℃) or NMR
436 103-104
437 75-79
438 194-195
439 68-69
440 111-112
441 74-78
442 1H NMR(200MHz，CHLOROFORM-D)d ppm 0.19-0.43(m，4H)，0.91-1.12(m，1H)，2.14(s， 3H)，2.74(t，J＝6.2Hz，4H)，3.77(t，J＝6.2Hz，2H)，3.80(d，J＝7.0Hz，2H)，7.45- 7.66(m，3H)，7.82-8.01(m，2H)，8.28-3.38(m，2H)，8.85-8.93(m，1H)
443 135-136.5
444 144-146
445 170-172
446 1H NMR(200MHz，CHLOROFORM-D)d ppm 4.63-4.75(m，2H)，5.05-5.27(m，2H)，5.65- 5.96(m，1H)，7.10-7.64(m，8H)，7.88-8.06(m，2H)
447 174-175.5
Table 11
Figure A20058003900502801
Table 11 (continuing)
Figure A20058003900502811
Table 11 (continuing)
Figure A20058003900502821
Table 11 (continuing)
Figure A20058003900502831
Table 11 (continuing)
Table 11 (continuing)
Figure A20058003900502851
Table 11 (continuing)
Figure A20058003900502861
Table 11 (continuing)
Figure A20058003900502871
Table 11 (continuing)
Figure A20058003900502881
Table 11 (continuing)
Figure A20058003900502891
Table 12
Figure A20058003900502901
Figure A20058003900502903
Table 12 (continuing)
Figure A20058003900502911
Figure A20058003900502912
Figure A20058003900502913
Table 12 (continuing)
Compound N o. MASS
1151 APCI(Pos)297(M+H)
1152 APCI(Pos)297(M+H)
1153 APCI(Pos)339(M+H)
1154 APCI(Pos)351(M+H)
1155 APCI(Pos)301(M+H)
1156 APCI(Pos)301(M+H)
1157 APCI(Pos)301(M+H)
1158 APCI(Pos)317(M+H)
1159 APCI(Pos)317(M+H)
1160 APCI(Pos)317(M+H)
1161 APCI(Pos)351(M+H)
1162 APCI(Pos)397(M+H)
1163 APCI(Pos)400(M+H)
1164 APCI(Pos)286(M+H)
1165 APCI(Pos)296(M+H)
1166 APCI(Pos)306(M+H)
1167 APCI(Pos)295(M+H)
1168 APCI(Pos)295(M+H)
1169 APCI(Pos)307(M+H)
1170 APCI(Pos)307(M+H)
1171 APCI(Pos)307(M+H)
1172 APCI(Pos)307(M+H)
1173 APCI(Pos)307(M+H)
1174 APCI(Pos)323(M+H)
1175 APCI(Pos)323(M+H)
Compound N o. MASS
1176 APCI(Pos)323(M+H)
1177 APCI(Pos)323(M+H)
1178 APCI(Pos)323(M+H)
1179 APCI(Pos)339(M+H)
1180 APCI(Pos)355(M+H)
1181 APCI(Pos)355(M+H)
1182 APCI(Pos)387(M+H)
1183 APCI(Pos)343(M+H)
1184 APCI(Pos)343(M+H)
1185 ESI(Pos)343(M+H)
1186 APCI(Pos)311(M+H)
1187 APCI(Pos)303(M+H)
1188 APCI(Pos)303(M+H)
1189 APCI(Pos)319(M+H)
1190 APCI(Pos)319(M+H)
1191 APCI(Pos)357(M+H)
1192 APCI(Pos)357(M+H)
1193 APCI(Pos)373(M+H)
1194 APCI(Pos)373(M+H)
1195 APCI(Pos)327(M+H)
1196 APCI(Pos)337(M+H)
1197 APCI(Pos)339(M+H)
1198 APCI(Pos)247(M+H)
1199 APCI(Pos)311(M+H)
1200 APCI(Pos)323(M+H)
Compound N o. MASS
1201 APCI(Pos)333(M+H)
1202 APCI(Pos)311(M+H)
1203 APCI(Pos)311(M+H)
1204 APCI(Pos)325(M+H)
1205 APCI(Pos)295(M+H)
1206 APCI(Pos)311(M+H)
1207 APCI(Pos)263(M+H)
1208 APCI(Pos)264(M+H)
1209 APCI(Pos)279(M+H)
1210 APCI(Pos)322(M+H)
1211 APCI(Pos)322(M+H)
1212 APCI(Pos)322(M+H)
1213 APCI(Pos)289(M+H)
1214 APCI(Pos)304(M+H)
1215 APCI(Pos)304(M+H)
1216 APCI(Pos)304(M+H)
1217 APCI(Pos)304(M+H)
1218 APCI(Pos)304(M+H)
1219 APCI(Pos)338(M+H)
1220 APCI(Pos)375(M+H)
Table 12 (continuing)
Compound N o. MASS
1221 APCI(Pos)310(M+H)
1222 APCI(Pos)310(M+H)
1223 APCI(Pos)311(M+H)
1224 APCI(Pos)311(M+H)
1225 APCI(Pos)327(M+H)
1226 APCI(Pos)327(M+H)
1227 APCI(Pos)311(M+H)
1228 APCI(Pos)311(M+H)
1229 APCI(Pos)311(M+H)
1230 APCI(Pos)311(M+H)
1231 APCI(Pos)312(M+H)
1232 APCI(Pos)328(M+H)
1233 APCI(Pos)329(M+H)
1234 ESI(Neg)322(M+H)
1235 APCI(Pos)355(M+H)
1236 APCI(Pos)389(M+H)
1237 APCI(Pos)437(M+H)
1238 APCI(Pos)358(M+H)
1239 APCI(Pos)471(M+H)
1240 APCI(Pos)325(M+H)
1241 APCI(Pos)325(M+H)
1242 APCI(Pos)325(M+H)
1243 APCI(Pos)368(M+H)
1244 APCI(Pos)394(M+H)
Compound N o. MASS
1245 APCI(Pos)396(M+H)
1246 APCI(Pos)408(M+H)
1247 APCI(Pos)408(M+H)
1248 APCI(Pos)410(M+H)
1249 APCI(Pos)410(M+H)
1250 APCI(Pos)368(M+H)
1251 APCI(Pos)387(M+H)
1252 APCI(Pos)401(M+H)
1253 APCI(Pos)417(M+H)
1254 APCI(Pos)417(M+H)
1255 APCI(Pos)421(M+H)
1256 APCI(Pos)432(M+H)
1257 APCI(Pos)432(M+H)
1258 APCI(Pos)446(M+H)
1259 APCI(Pos)341(M+H)
1260 APCI(Pos)341(M+H)
1261 APCI(Pos)341(M+H)
1262 APCI(Pos)355(M+H)
1263 APCI(Pos)383(M+H)
1264 APCI(Pos)392(M+H)
1265 APCI(Pos)403(M+H)
1266 APCI(Pos)404(M+H)
1267 APCI(Pos)409(M+H)
1268 APCI(Pos)424(M+H)
Compound N o. MASS
1269 APCI(Pos)369(M+H)
1270 APCI(Pos)405(M+H)
1271 APCI(Pos)361(M+H)
1272 APCI(Pos)361(M+H)
1273 APCI(Pos)405(M+H)
1274 APCI(Pos)405(M+H)
1275 APCI(Pos)405(M+H)
1276 APCI(Pos)372(M+H)
1277 APCI(Pos)384(M+H)
1278 APCI(Pos)371(M+H)
1279 APCI(Pos)357(M+H)
1280 APCI(Pos)405(M+H)
1281 APCI(Pos)325(M+H)
1282 APCI(Pos)325(M+H)
1283 APCI(Pos)325(M+H)
1284 APCI(Pos)325(M+H)
1285 APCI(Pos)325(M+H)
1286 APCI(Pos)339(M+H)
1287 APCI(Pos)339(M+H)
1288 APCI(Pos)339(M+H)
1289 APCI(Pos)387(M+H)
1290 APCI(Pos)387(M+H)
1291 APCI(Pos)405(M+H)
1292 APCI(Pos)417(M+H)
Table 12 (continuing)
Compound N o. MASS
1293 APCI(Pos)345(M+H)
1294 APCI(Pos)356(M+H)
1295 APCI(Pos)356(M+H)
1296 APCI(Pos)388(M+H)
1297 APCI(Pos)388(M+H)
1298 APCI(Pos)388(M+H)
1299 APCI(Pos)326(M+H)
1300 APCI(Pos)326(M+H)
1301 APCI(Pos)326(M+H)
1302 APCI(Pos)342(M+H)
1303 APCI(Pos)342(M+H)
1304 APCI(Pos)405(M+H)
1305 APCI(Pos)405(M+H)
1306 APCI(Pos)410(M+H)
1307 APCI(Pos)418(M+H)
1308 APCI(Pos)438(M+H)
1309 APCI(Pos)404(M+H)
1310 APCI(Pos)343(M+H)
1311 APCI(Pos)405(M+H)
1312 APCI(Pos)419(M+H)
1313 APCI(Pos)415(M+H)
1314 APCI(Pos)431(M+H)
1315 APCI(Pos)489(M+H)
1316 APCI(Pos)339(M+H)
Compound N o. MASS
1317 APCI(Pos)339(M+H)
1318 APCI(Pos)381(M+H)
1319 APCI(Pos)393(M+H)
1320 APCI(Pos)424(M+H)
1321 APCI(Pos)419(M+H)
1322 APCI(Pos)515(M+H)
1323 APCI(Pos)391(M+H)
1324 APCI(Pos)435(M+H)
1325 APCI(Pos)439(M+H)
1326 APCI(Pos)448(M+H)
1327 APCI(Pos)463(M+H)
1328 APCI(Pos)489(M+H)
1329 APCI(Pos)500(M+H)
1330 APCI(Pos)339(M+H)
1321 APCI(Pos)339(M+H)
1332 APCI(Pos)339(M+H)
1333 APCI(Pos)353(M+H)
1334 APCI(Pos)353(M+H)
1335 APCI(Pos)353(M+H)
1336 APCI(Pos)353(M+H)
1337 APCI(Pos)353(M+H)
1338 APCI(Pos)367(M+H)
1339 APCI(Pos)367(M+H)
1340 APCI(Pos)367(M+H)
Compound N o. MASS
1341 APCI(Pos)381(M+H)
1342 APCI(Pos)393(M+H)
1343 APCI(Pos)393(M+H)
1344 APCI(Pos)393(M+H)
1345 APCI(Pos)457(M+H)
1346 APCI(Pos)525(M+H)
1347 APCI(Pos)415(M+H)
1348 APCI(Pos)401(M+H)
1349 APCI(Pos)401(M+H)
1350 APCI(Pos)415(M+H)
1351 APCI(Pos)419(M+H)
1352 APCI(Pos)429(M+H)
1353 APCI(Pos)455(M+H)
1354 APCI(Pos)339(M+H)
1355 APCI(Pos)359(M+H)
1356 APCI(Pos)359(M+H)
1357 APCI(Pos)359(M+H)
1358 APCI(Pos)373(M+H)
1359 APCI(Pos)373(M+H)
1360 APCI(Pos)403(M+H)
1361 APCI(Pos)403(M+H)
1362 APCI(Pos)417(M+H)
1363 APCI(Pos)340(M+H)
1364 APCI(Pos)340(M+H)
Table 12 (continuing)
Compound N o. MASS
1365 APCI(Pos)384(M+H)
1366 APCI(Pos)402(M+H)
1367 APCI(Pos)402(M+H)
1368 APCI(Pos)420(M+H)
1369 APCI(Pos)436(M+H)
1370 APCI(Pos)454(M+H)
1371 APCI(Pos)470(M+H)
1372 APCI(Pos)419(M+H)
1373 APCI(Pos)419(M+H)
1374 APCI(Pos)420(M+H)
1375 APCI(Pos)460(M+H)
1376 APCI(Pos)356(M+H)
1377 APCI(Pos)410(M+H)
1378 APCI(Pos)396(M+H)
1379 APCI(Pos)402(M+H)
1380 APCI(Pos)340(M+H)
1381 APCI(Pos)429(M+H)
1382 APCI(Pos)378(M+H)
1383 APCI(Pos)434(M+H)
1384 APCI(Pos)448(M+H)
1385 APCI(Pos)380(M+H)
1386 APCI(Pos)413(M+H)
1387 APCI(Pos)467(M+H)
1388 APCI(Pos)429(M+H)
Compound N o. MASS
1389 APCI(Pos)353(M+H)
1390 APCI(Pos)373(M+H)
1391 APCI(Pos)387(M+H)
1392 APCI(Pos)417(M+H)
1393 APCI(Pos)417(M+H)
1394 APCI(Pos)427(M+H)
1395 APCI(Pos)431(M+H)
1396 APCI(Pos)373(M+H)
1397 APCI(Pos)374(M+H)
1398 APCI(Pos)374(M+H)
1399 APCI(Pos)374(M+H)
1400 APCI(Pos)388(M+H)
1401 APCI(Pos)390(M+H)
1402 APCI(Pos)376(M+H)
1403 APCI(Pos)378(M+H)
1404 APCI(Pos)390(M+H)
1405 APCI(Pos)444(M+H)
1406 APCI(Pos)405(M+H)
1407 APCI(Pos)420(M+H)
1408 APCI(Pos)361(M+H)
1409 APCI(Pos)361(M+H)
1410 APCI(Pos)361(M+H)
1411 APCI(Pos)375(M+H)
1412 APCI(Pos)395(M+H)
Compound N o. MASS
1413 APCI(Pos)396(M+H)
1414 APCI(Pos)390(M+H)
1415 APCI(Pos)444(M+H)
1416 APCI(Pos)427(M+H)
1417 APCI(Pos)381(M+H)
1418 APCI(Pos)361(M+H)
1419 APCI(Pos)375(M+H)
1420 APCI(Pos)391(M+H)
1421 APCI(Pos)405(M+H)
1422 APCI(Pos)379(M+H)
1423 APCI(Pos)367(M+H)
1424 APCI(Pos)381(M+H)
1425 APCI(Pos)377(M+H)
1426 APCI(Pos)377(M+H)
1427 APCI(Pos)391(M+H)
1428 APCI(Pos)411(M+H)
1429 APCI(Pos)425(M+H)
1430 APCI(Pos)383(M+H)
1431 APCI(Pos)362(M+H)
Table 13
Compound N o. MASS
2001 APCI：267(M+H)+
2002 APCI：267(M+H)+
2003 APCI：293(M+H)+
2004 APCI：297(M+H)+
2005 APCI：301(M+H)+
2006 APCI：301(M+H)+
2007 APCI：302(M+H)+
2008 APCI：302(M+H)+
2009 APCI：305(M+H)+
2010 APCI：306(M+H)+
2011 APCI：307(M+H)+
2012 APCI：307(M+H)+
2013 APCI：312(M+H)+
2014 APCI：315(M+H)+
2015 APCI：315(M+H)+
2016 APCI：315(M+H)+
2017 APCI：316(M+H)+
2018 APCI：317(M+H)+
2019 APCI：319(M+H)+
2020 APCI：319(M+H)+
2021 APCI：321(M+H)+
2022 APCI：322(M+H)+
2023 APCI：323(M+H)+
2024 APCI：323(M+H)+
2025 APCI：323(M+H)+
2026 APCI：323(M+H)+
2027 APCI：323(M+H)+
2028 APCI：327(M+H)+
2029 APCI：330(M+H)+
2030 APCI：331(M+H)+
2031 APCI：331(M+H)+
2032 APCI：332(M+H)+
2033 APCI：333(M+H)+
2034 APCI：335(M+H)+
2035 APCI：335(M+H)+
2036 APCI：337(M+H)+
2037 APCI：337(M+H)+
2038 APCI：337(M+H)+
2039 APCI：338(M+H)+
2040 APCI：338(M+H)+
Compound N o. MASS
2041 APCI：338(M+H)+
2042 APCI：338(M+H)+
2043 APCI：339(M+H)+
2044 APCI：339(M+H)+
2045 APCI：339(M+H)+
2046 APCI：339(M+H)+
2047 APCI：341(M+H)+
2048 APCI：341(M+H)+
2049 APCI：341(M+H)+
2050 APCI：347(M+H)+
2051 APCI：347(M+H)+
2052 APCI：351(M+H)+
2053 APCI：353(M+H)+
2054 APCI：353(M+H)+
2055 APCI：355(M+H)+
2056 APCI：355(M+H)+
2057 APCI：355(M+H)+
2058 APCI：356(M+H)+
2059 APCI：356(M+H)+
2060 APCI：356(M+H)+
2061 APCI：356(M+H)+
2062 APCI：357(M+H)+
2063 APCI：366(M+H)+
2064 APCI：366(M+H)+
2065 APCI：369(M+H)+
2066 APCI：371(M+H)+
2067 APCI：372(M+H)+
2068 APCI：372(M+H)+
2069 APCI：373(M+H)+
2070 APCI：375(M+H)+
2071 APCI：375(M+H)+
2072 APCI：379(M+H)+
2073 APCI：379(M+H)+
2074 APCI：379(M+H)+
2075 APCI：383(M+H)+
2076 APCI：383(M+H)+
2077 APCI：389(M+H)+
2078 APCI：395(M+H)+
2079 APCI：403(M+H)+
2080 APCI：406(M+H)+
Table 13 (continuing)
Chemical combination No. MASS
2081 APCI：407(M+H)+
2082 APCI：412(M+H)+
2083 APCI：413(M+H)+
2084 APCI：427(M+H)+
2085 APCI：431(M+H)+
2086 APCI：269(M+H)+
2087 APCI：269(M+H)+
2088 APCI：283(M+H)+
2089 APCI：295(M+H)+
2090 APCI：295(M+H)+
2091 APCI：299(M+H)+
2092 APCI：304(M+H)+
2092 APCI：304(M+H)+
2094 APCI：304(M+H)+
2095 APCI：307(M+H)+
2096 APCI：308(M+H)+
2097 APCI：309(M+H)+
2098 APCI：309(M+H)+
2099 APCI：317(M+H)+
2100 APCI：317(M+H)+
2101 APCI：317(M+H)+
2102 APCI：317(M+H)+
2103 APCI：317(M+H)+
2104 APCI：318(M+H)+
2105 APCI：319(M+H)+
2106 APCI：321(M+H)+
2107 APCI：321(M+H)+
2108 APCI：323(M+H)+
2109 APCI：324(M+H)+
2110 APCI：325(M+H)+
2111 APCI：325(M+H)+
2112 APCI：325(M+H)+
2113 APCI：325(M+H)+
2114 APCI：325(M+H)+
2115 APCI：329(M+H)+
2116 APCI：331(M+H)+
2117 APCI：333(N+H)+
2118 APCI：333(M+H)+
2119 APCI：334(M+H)+
2120 APCI：335(M+H)+
Compound N o. MASS
2121 APCI：337(M+H)+
2122 APCI：337(M+H)+
2123 APCI：337(M+H)+
2124 APCI：339(M+H)+
2125 APCI：339(M+H)+
2126 APCI：340(M+H)+
2127 APCI：340(M+H)+
2128 APCI：340(M+H)+
2129 APCI：340(M+H)+
2130 APCI：341(M+H)+
2131 APCI：341(M+H)+
2132 APCI：341(M+H)+
2133 APCI：341(M+H)+
2134 APCI：343(M+H)+
2135 APCI：343(M+H)+
2136 APCI：349(M+H)+
2137 APCI：349(M+H)+
2138 APCI：355(M+H)+
2139 APCI：355(M+H)+
2140 APCI：357(M+H)+
2141 APCI：357(M+H)+
2142 APCI：357(M+H)+
2143 APCI：358(M+H)+
2144 APCI：358(M+H)+
2145 APCI：358(M+H)+
2146 APCI：358(M+H)+
2147 APCI：358(M+H)+
2148 APCI：359(M+H)+
2149 APCI：368(M+H)+
2150 APCI：368(M+H)+
2151 APCI：371(M+H)+
2152 APCI：373(M+H)+
2153 APCI：374(M+H)+
2154 APCI：375(M+H)+
2155 APCI：375(M+H)+
2156 APCI：377(M+H)+
2157 APCI：377(M+H)+
2158 APCI：379(M+H)+
2159 APCI：381(M+H)+
2160 APCI：381(M+H)+
Table 13 (continuing)
Compound N o. MASS
2161 APCI：381(M+H)+
2162 APCI：385(M+H)+
2163 APCI：385(M+H)+
2164 APCI：391(M+H)+
2165 APCI：397(M+H)+
2166 APCI：405(M+H)+
2167 APCI：408(M+H)+
2168 APCI：414(M+H)+
2169 APCI：415(M+H)+
2170 APCI：429(M+H)+
2171 APCI：433(M+H)+
2172 APCI：283(M+H)+
2173 APCI：283(M+H)+
2174 APCI：297(M+H)+
2175 APCI：309(M+H)+
2176 APCI：313(M+H)+
2177 APCI：317(M+H)+
2178 APCI：317(M+H)+
2179 APCI：318(M+H)+
2180 APCI：318(M+H)+
2181 APCI：321(M+H)+
2182 APCI：322(M+H)+
2183 APCI：323(M+H)+
2184 APCI：323(M+H)+
2185 APCI：328(M+H)+
2186 APCI：331(M+H)+
2187 APCI：331(M+H)+
2188 APCI：331(M+H)+
2189 APCI：331(M+H)+
2190 APCI：332(M+H)+
2191 APCI：333(M+H)+
2192 APCI：335(M+H)+
2193 APCI：335(M+H)+
2194 APCI：337(M+H)+
2195 APCI；337(M+H)+
2196 APCI：338(M+H)+
2197 APCI：339(M+H)+
2198 APCI：339(M+H)+
2199 APCI：339(M+H)+
2200 APCI：339(M+H)+
Compound N o. MASS
2201 APCI：339(M+H)+
2202 APCI：339(M+H)+
2203 APCI：343(M+H)+
2204 APCI：345(M+H)+
2205 APCI：346(M+H)+
2206 APCI：347(M+H)+
2207 APCI：347(M+H)+
2208 APCI：348(M+H)+
2209 APCI：349(M+H)+
2210 APCI：351(M+H)+
2211 APCI：351(M+H)+
2212 APCI：353(M+H)+
2213 APCI：353(M+H)+
2214 APCI：353(M+H)+
2215 APCI：354(M+H)+
2216 APCI：354(M+H)+
2217 APCI：354(M+H)+
2218 APCI：354(M+H)+
2219 APCI：355(M+H)+
2220 APCI：355(M+H)+
2221 APCI：355(M+H)+
2222 APCI：355(M+H)+
2223 APCI：355(M+H)+
2224 APCI：355(M+H)+
2225 APCI：357(M+H)+
2226 APCI：357(M+H)+
2227 APCI：357(M+H)+
2228 APCI：363(M+H)+
2229 APCI：363(M+H)+
2230 APCI：363(M+H)+
2231 APCI：369(M+H)+
2232 APCI：369(M+H)+
2233 APCI：371(M+H)+
2234 APCI：371(M+H)+
2235 APCI：371(M+H)+
2236 APCI：372(M+H)+
2237 APCI：372(M+H)+
2238 APCI：372(M+H)+
2239 APCI：372(M+H)+
2240 APCI：373(M+H)+
Table 13 (continuing)
Compound N o. MASS
2241 APCI：381(M+H)+
2242 APCI：381(M+H)+
2243 APCI：382(M+H)+
2244 APCI：382(M+H)+
2245 APCI：385(M+H)+
2246 APCI：387(M+H)+
2247 APCI：388(M+H)+
2248 APCI：388(M+H)+
2249 APCI：389(M+H)+
2250 APCI：389(M+H)+
2251 APCI：389(M+H)+
2252 APCI：391(M+H)+
2253 APCI：391(M+H)+
2254 APCI：393(M+H)+
2255 APCI：395(M+H)+
2256 APCI：395(M+H)+
2257 APCI：395(M+H)+
2258 APCI：399(M+H)+
2259 APCI：405(M+H)+
2260 APCI：411(M+H)+
2261 APCI：419(M+H)+
2262 APCI：429(M+H)+
2263 APCI：428(M+H)+
2264 APCI：429(M+H)+
2265 APCI：429(M+H)+
2266 APCI：443(M+H)+
2267 APCI：313(M+H)+
2268 APCI：313(M+H)+
2269 APCI：327(M+H)+
2270 APCI：339(M+H)+
2271 APCI：339(M+H)+
2272 APCI：343(M+H)+
2273 APCI：347(M+H)+
2274 APCI：347(M+H)+
2275 APCI：348(M+H)+
2276 APCI：348(M+H)+
2277 APCI：351(M+H)+
2278 APCI：352(M+H)+
2279 APCI：353(M+H)+
2280 APCI：353(M+H)+
Compound N o. MASS
2281 APCI：358(M+H)+
2282 APCI：361(M+H)+
2283 APCI：361(M+H)+
2284 APCI：361(M+H)+
2285 APCI：361(M+H)+
2286 APCI：361(M+H)+
2287 APCI：362(M+H)+
2288 APCI：363(M+H)+
2289 APCI：365(M+H)+
2290 APCI：365(M+H)+
2291 APCI：367(M+H)+
2292 APCI：367(M+H)+
2293 APCI：368(M+H)+
2294 APCI：369(M+H)+
2295 APCI：369(M+H)+
2296 APCI：369(M+H)+
2297 APCI：369(M+H)+
2298 APCI：369(M+H)+
2299 APCI：369(M+H)+
2300 APCI：373(M+H)+
2301 APCI：375(M+H)+
2302 APCI：376(M+H)+
2303 APCI：377(M+H)+
2304 APCI：377(M+H)+
2305 APCI：378(M+H)+
2306 APCI：379(M+H)+
2307 APCI：381(M+H)+
2308 APCI：381(M+H)+
2309 APCI：381(M+H)+
2310 APCI：381(M+H)+
2311 APCI：383(M+H)+
2312 APCI：383(M+H)+
2313 APCI：383(M+H)+
2314 APCI：384(M+H)+
2315 APCI：384(M+H)+
2316 APCI：384(M+H)+
2317 APCI：384(M+H)+
2318 APCI：385(M+H)+
2319 APCI：385(M+H)+
2320 APCI：385(M+H)+
Table 13 (continuing)
Compound N o. MASS
2321 APCI：385(M+H)+
2322 APCI：385(M+H)+
2323 APCI：387(M+H)+
2324 APCI：387(M+H)+
2325 APCI：387(M+H)+
2326 APCI：393(M+H)+
2327 APCI：393(M+H)+
2328 APCI：393(M+H)+
2329 APCI：397(M+H)+
2330 APCI：397(M+H)+
2331 APCI：399(M+H)+
2332 APCI：399(M+H)+
2333 APCI：401(M+H)+
2334 APCI：401(M+H)+
2335 APCI：401(M+H)+
2336 APCI：401(M+H)+
2337 APCI：401(M+H)+
2338 APCI：402(M+H)+
2339 APCI：402(M+H)+
2340 APCI：402(M+H)+
2341 APCI：402(M+H)+
2342 APCI：402(M+H)+
2343 APCI：401(M+H)+
2344 APCI：403(M+H)+
2345 APCI：411(M+H)+
2346 APCI：412(M+H)+
2347 APCI：412(M+H)+
2348 APCI：417(M+H)+
2349 APCI：417(M+H)+
2350 APCI：418(M+H)+
2351 APCI：418(M+H)+
2352 APCI：419(M+H)+
2353 APCI：419(M+H)+
2354 APCI：419(M+H)+
2355 APCI：419(M+H)+
2356 APCI：419(M+H)+
2357 APCI：421(M+H)+
2358 APCI：421(M+H)+
2359 APCI：423(M+H)+
2360 APCI：425(M+H)+
Compound N o. MASS
2361 APCI：425(M+H)+
2362 APCI：425(M+H)+
2363 APCI：425(M+H)+
2364 ESI：429(M+H)+
2365 APCI：429(M+H)+
2366 APCI：429(M+H)+
2367 APCI：435(M+H)+
2368 APCI：441(M+H)+
2369 APCI：452(M+H)+
2370 APCI：453(M+H)+
2371 APCI：458(M+H)+
2372 APCI：459(M+H)+
2373 APCI：473(M+H)+
2374 APCI：477(M+H)+
2375 APCI：257(M+H)+
2376 APCI：261(M+H)+
2377 APCI：293(M+H)+
2378 APCI：295(M+H)+
2379 APCI：295(M+H)+
2380 APCI：297(M+H)+
2381 APCI：307(M+H)+
2382 APCI：309(M+H)+
2383 APCI：309(M+H)+
2384 APCI：309(M+H)+
2385 APCI：310(M+H)+
2386 APCI：319(M+H)+
2387 APCI：319(M+H)+
2388 APCI：320(M+H)+
2389 APCI：321(M+H)+
2390 APCI：323(M+H)+
2391 APCI：323(M+H)+
2392 APCI：323(M+H)+
2393 APCI：323(M+H)+
2394 APCI：325(M+H)+
2395 APCI：327(M+H)+
2396 APCI：330(M+H)+
2397 APCI：331(M+H)+
2398 APCI：331(M+H)+
2399 APCI：331(M+H)+
2400 APCI：332(M+H)+
Table 13 (continuing)
Compound N o. MASS
2401 APCI：333(M+H)+
2402 APCI：333(M+H)+
2403 APCI：334(M+H)+
2404 APCI：335(M+H)+
2405 APCI：335(M+H)+
2406 APCI：336(M+H)+
2407 APCI：337(M+H)+
2408 APCI：338(M+H)+
2409 APCI：339(M+H)+
2410 APCI：339(M+H)+
2411 APCI：344(M+H)+
2412 APCI：344(M+H)+
2413 APCI：344(M+H)+
2414 APCI：345(M+H)+
2415 APCI：345(M+H)+
2416 APCI：346(M+H)+
2417 APCI：346(M+H)+
2418 APCI：346(M+H)+
2419 APCI：346(M+H)+
2420 APCI：347(M+H)+
2421 APCI：347(M+H)+
2422 APCI：347(M+H)+
2423 APCI：347(M+H)+
2424 APCI：347(M+H)+
2425 APCI：347(M+H)+
2426 APCI：348(M+H)+
2427 APCI：348(M+H)+
2428 APCI：349(M+H)+
2429 APCI：350(M+H)+
2430 APCI：351(M+H)+
2431 APCI：351(M+H)+
2432 APCI：351(M+H)+
2433 APCI：353(M+H)+
2434 APCI：354(M+H)+
2435 APCI：355(M+H)+
2436 APCI：355(M+H)+
2437 APCI：355(M+H)+
2438 APCI：357(M+H)+
2439 APCI：357(M+H)+
2440 APCI：357(M+H)+
Compound N o. MASS
2441 APCI：358(M+H)+
2442 APCI：359(M+H)+
2443 APCI：359(M+H)+
2444 APCI：359(M+H)+
2445 APCI：360(M+H)+
2446 ESI：360(M+H)+
2447 APCI：361(M+H)+
2448 APCI：361(M+H)+
2449 APCI：361(M+H)+
2450 APCI：361(M+H)+
2451 APCI：361(M+H)+
2452 APCI：364(M+H)+
2453 APCI：364(M+H)+
2454 APCI：364(M+H)+
2455 APCI：364(M+H)+
2456 APCI：365(M+H)+
2457 APCI：367(M+H)+
2458 APCI：368(M+H)+
2459 APCI：369(M+H)+
2460 APCI：369(M+H)+
2461 APCI：369(M+H)+
2462 APCI：369(M+H)+
2463 APCI：369(M+H)+
2464 APCI：369(M+H)+
2465 APCI：369(M+H)+
2466 APCI：371(M+H)+
2467 APCI：371(M+H)+
2468 APCI：371(M+H)+
2469 APCI：371(M+H)+
2470 APCI：372(M+H)+
2471 APCI：373(M+H)+
2472 APCI：373(M+H)+
2473 APCI：373(M+H)+
2474 APCI：373(M+H)+
2475 APCI：373(M+H)+
2476 APCI：373(M+H)+
2477 APCI：374(M+H)+
2478 APCI：374(M+H)+
2479 APCI：374(M+H)+
2480 APCI：375(M+H)+
Table 13 (continuing)
Compound N o. MASS
2481 APCI：375(M+H)+
2482 APCI：376(M+H)+
2483 APCI：376(M+H)+
2484 APCI：377(M+H)+
2485 APCI：378(M+H)+
2486 APCI：378(M+H)+
2487 APCI：379(M+H)+
2488 APCI：379(M+H)+
2489 APCI：379(M+H)+
2490 APCI：380(M+H)+
2491 APCI：381(M+H)+
2492 APCI：381(M+H)+
2493 APCI：381(M+H)+
2494 APCI：381(M+H)+
2495 APCI：381(M+H)+
2496 APCI：381(M+H)+
2497 APCI：381(M+H)+
2498 APCI：382(M+H)+
2499 APCI：382(M+H)+
2500 APCI：382(M+H)+
2501 APCI：383(M+H)+
2502 APCI：383(M+H)+
2503 APCI：383(M+H)+
2504 APCI：383(M+H)+
2505 APCI：384(M+H)+
2506 APCI：385(M+H)+
2507 APCI：385(M+H)+
2508 APCI：385(M+H)+
2509 APCI：385(M+H)+
2510 APCI：386(M+H)+
2511 APCI：387(M+H)+
2512 APCI：387(M+H)+
2513 APCI：387(M+H)+
2514 APCI：387(M+H)+
2515 APCI：387(M+H)+
2516 APCI：387(M+H)+
2517 APCI：387(M+H)+
2518 APCI：388(M+H)+
2519 APCI：389(M+H)+
2520 APCI：389(M+H)+
Compound N o. MASS
2521 APCI：389(M+H)+
2522 APCI：389(M+H)+
2523 APCI：389(M+H)+
2524 APCI：389(M+H)+
2525 APCI：389(M+H)+
2526 APCI：389(M+H)+
2527 APCI：390(M+H)+
2528 APCI：390(M+H)+
2529 APCI：390(M+H)+
2530 APCI：393(M+H)+
2531 PPCI：393(M+H)+
2532 APCI：395(M+H)+
2533 APCI：395(M+H)+
2534 APCI：395(M+H)+
2535 APCI：395(M+H)+
2536 APCI：395(M+H)+
2537 APCI：395(M+H)+
2538 APCI：396(M+H)+
2539 APCI：396(M+H)+
2540 APCI：397(M+H)+
2541 APCI：397(M+H)+
2542 APCI：397(M+H)+
2543 APCI：397(M+H)+
2544 APCI：397(M+H)+
2545 APCI：397(M+H)+
2546 APCI：397(M+H)+
2547 APCI：398(M+H)+
2548 APCI：398(M+H)+
2549 APCI：398(M+H)+
2550 APCI：398(M+H)+
2551 APCI：398(M+H)+
2552 APCI：398(M+H)+
2553 ESI：399(M+H)+
2554 APCI：399(M+H)+
2555 APCI：399(M+H)+
2556 APCI：399(M+H)+
2557 APCI：401(M+H)+
2558 APCI：401(M+H)+
2559 APCI：401(M+H)+
2560 APCI：401(M+H)+
Table 13 (continuing)
Compound N o. MASS
2561 APCI：401(M+H)+
2562 APCI：403(M+H)+
2563 APCI：403(M+H)+
2564 APCI：403(M+H)+
2565 APCI：404(M+H)+
2566 APCI：404(M+H)+
2567 APCI：404(M+H)+
2568 APCI：404(M+H)+
2569 APCI：405(M+H)+
2570 APCI：405(M+H)+
2571 APCI：406(M+H)+
2572 APCI：408(M+H)+
2573 APCI：408(M+H)+
2574 ESI：409(M+H)+
2575 APCI：410(M+H)+
2576 APCI：410(M+H)+
2577 APCI：410(M+H)+
2278 APCI：411(M+H)+
2579 APCI：412(M+H)+
2580 APCI：412(M+H)+
2581 APCI：412(M+H)+
2582 APCI：412(M+H)+
2583 APCI：412(M+H)+
2584 APCI：413(M+H)+
2585 APCI：413(M+H)+
2586 APCI：413(M+H)+
2587 APCI：413(M+H)+
2588 APCI：413(M+H)+
2589 APCI：414(M+H)+
2590 APCI：415(M+H)+
2591 APCI：415(M+H)+
2592 APCI：415(M+H)+
2593 APCI：415(M+H)+
2594 APCI：415(M+H)+
2595 APCI：415(M+H)+
2596 APCI：415(M+H)+
2597 APCI：416(M+H)+
2598 APCI：417(M+H)+
2599 APCI：417(M+H)+
2600 APCI：418(M+H)+
Compound N o. MASS
2601 APCI：418(M+H)+
2602 APCI：419(M+H)+
2603 APCI：419(M+H)+
2604 APCI：419(M+H)+
2605 APCI：419(M+H)+
2606 APCI：419(M+H)+
2607 APCI：421(M+H)+
2608 APCI：421(M+H)+
2609 APCI：421(M+H)+
2610 APCI：421(M+H)+
2611 APCI：422(M+H)+
2612 APCI：422(M+H)+
2613 APCI：423(M+H)+
2614 APCI：425(M+H)+
2615 APCI：427(M+H)+
2616 APCI：427(M+H)+
2617 APCI：427(M+H)+
2618 APCI：427(M+H)+
2619 APCI：427(M+H)+
2620 APCI：427(M+H)+
2621 APCI：428(M+H)+
2622 APCI：428(M+H)+
2623 APCI：428(M+H)+
2624 APCI：429(M+H)+
2625 APCI：429(M+H)+
2626 APCI：429(M+H)+
2627 APCI：431(M+H)+
2628 APCI：431(M+H)+
2629 APCI：431(M+H)+
2630 APCI：432(M+H)+
2631 APCI：432(M+H)+
2632 APCI：435(M+H)+
2633 APCI：437(M+H)+
2634 APCI：437(M+H)+
2635 APCI：438(M+H)+
2636 APCI：439(M+H)+
2637 APCI：439(M+H)+
2638 APCI：439(M+H)+
2639 APCI：440(M+H)+
2640 APCI：441(M+H)+
Table 13 (continuing)
Compound N o. MASS
2641 APCI：443(M+H)+
2642 APCI：444(M+H)+
2643 APCI：444(M+H)+
2644 APCI：448(M+H)+
2645 APCI：449(M+H)+
2646 APCI：449(M+H)+
2647 APCI：449(M+H)+
2648 APCI：453(M+H)+
2649 APCI：454(M+H)+
2650 APCI：455(M+H)+
2651 APCI：455(M+H)+
2652 APCI：456(M+H)+
2653 APCI：457(M+H)+
2654 APCI：459(M+H)+
2655 APCI：462(M+H)+
2656 APCI：462(M+H)+
2657 APCI：462(M+H)+
2658 APCI：463(M+H)+
2659 APCI：465(M+H)+
2660 APCI：465(M+H)+
2661 APCI：465(M+H)+
2662 APCI：471(M+H)+
2663 APCI：475(M+H)+
2664 APCI：476(M+H)+
2665 APCI：477(M+H)+
2666 APCI：478(M+H)+
2667 APCI：482(M+H)+
2668 APCI：483(M+H)+
2669 APCI：492(M+H)+
2670 APCI：494(M+H)+
2671 APCI：495(M+H)+
2672 APCI：497(M+H)+
2673 APCI：497(M+H)+
2674 APCI：498(M+H)+
2675 APCI：508(M+H)+
2676 APCI：523(M+H)+
2677 APCI：531(M+H)+
2678 APCI：533(M+H)+
Table 14
No. MASS
3001 ESI(Pos)250(M+H)
3002 ESI(Pos)264(M+H)
3003 ESI(Pos)278(M+H)
3004 ESI(Pos)278(M+H)
3005 ESI(Pos)292(M+H)
3006 ESI(Pos)292(M+H)
3007 ESI(Pos)292(M+H)
3008 ESI(Pos)306(M+H)
3009 ESI(Pos)306(M+H)
3010 ESI(Pos)306(M+H)
3011 ESI(Pos)290(M+H)
3012 ESI(Pos)318(M+H)
3013 ESI(Pos)332(M+H)
3014 ESI(Pos)326(M+H)
3015 ESI(Pos)340(M+H)
3016 ESI(Pos)354(M+H)
3017 ESI(Pos)402(M+H)
3018 ESI(Neg)330(M+H)
3019 ESI(Pos)342(M+H)
3020 ESI(Pos)356(M+H)
3021 ESI(Pos)280(M+H)
3022 ESI(Pos)340(M+H)
3023 ESI(Pos)356(M+H)
3024 ESI(Pos)356(M+H)
3025 ESI(Pos)310(M+H)
3026 ESI(Pos)308(M+H)
3027 ESI(Pos)384(M+H)
3028 ESI(Pos)404(M+H)
3029 ESI(Pos)338(M+H)
3030 ESI(Pos)280(M+H)
3031 ESI(Pos)310(M+H)
3032 ESI(Pos)321(M+H)
3033 ESI(Pos)322(M+H)
3034 ESI(Pos)276(M+H)
3035 ESI(Pos)290(M+H)
3036 ESI(Pos)304(M+H)
3037 ESI(Pos)318(M+H)
3038 ESI(Pos)370(M+H)
3039 ESI(Pos)352(M+H)
3040 ESI(Pos)414(M+H)
No. MASS
3041 ESI(Pos)312(M+H)
3042 ESI(Pos)326(M+H)
3043 ESI(Pos)326(M+H)
3044 ESI(Pos)326(M+H)
3045 ESI(Pos)330(M+H)
3046 ESI(Pos)330(M+H)
3047 ESI(Pos)330(M+H)
3048 ESI(Pos)337(M+H)
3049 ESI(Pos)337(M+H)
3050 ESI(Pos)340(M+H)
3051 ESI(Pos)340(M+H)
3052 ESI(Pos)340(M+H)
3053 ESI(Pos)342(M+H)
3054 ESI(Pos)342(M+H)
3055 ESI(Pos)344(M+H)
3056 ESI(Pos)344(M+H)
3057 ESI(Pos)346(M+H)
3058 ESI(Pos)346(M+H)
3059 ESI(Pos)346(M+H)
3060 ESI(Pos)348(M+H)
3061 ESI(Pos)348(M+H)
3062 ESI(Pos)348(M+H)
3063 ESI(Pos)348(M+H)
3064 ESI(Pos)348(M+H)
3065 ESI(Pos)348(M+H)
3066 ESI(Pos)354(M+H)
3067 ESI(Pos)354(M+H)
3068 ESI(Pos)356(M+H)
3069 ESI(Pos)357(M+H)
3070 ESI(Pos)362(M+H)
3071 ESI(Pos)362(M+H)
3072 ESI(Pos)362(M+H)
3073 ESI(Pos)362(M+H)
3074 ESI(Pos)364(M+H)
3075 ESI(Pos)364(M+H)
3076 ESI(Pos)364(M+H)
3077 ESI(Pos)364(M+H)
3078 ESI(Pos)364(M+H)
3079 ESI(Pos)366(M+H)
3080 ESI(Pos)366(M+H)
Table 14 (continuing)
No. MASS
3081 ESI(Pos)366(M+H)
3082 ESI(Pos)366(M+H)
3083 ESI(Pos)368(M+H)
3084 ESI(Pos)392(M+H)
3085 ESI(Pos)372(M+H)
3086 ESI(Pos)378(M+H)
3087 ESI(Pos)378(M+H)
3088 ESI(Pos)380(M+H)
3089 ESI(Pos)380(M+H)
3090 ESI(Neg)378(M+H)
3091 ESI(Pos)380(M+H)
3092 ESI(Pos)380(M+H)
3093 ESI(Pos)382(M+H)
3094 ESI(Pos)382(M+H)
3095 ESI(Pos)382(M+H)
3096 ESI(Pos)384(M+H)
3097 ESI(Pos)388(M+H)
3098 ESI(Pos)390(M+H)
3099 ESI(Pos)390(M+H)
3100 ESI(Pos)390(M+H)
3101 ESI(Pos)396(M+H)
3102 ESI(Pos)396(M+H)
3103 ESI(Pos)396(M+H)
3104 ESI(Pos)398(M+H)
3105 ESI(Pos)398(M+H)
3106 ESI(Pos)398(M+H)
3107 ESI(Pos)398(M+H)
3108 ESI(Pos)398(M+H)
3109 ESI(Pos)398(M+H)
3110 ESI(Pos)398(M+H)
3111 ESI(Pos)400(M+H)
3112 ESI(Pos)402(M+H)
3113 ESI(Pos)402(M+H)
3114 ESI(Pos)404(M+H)
3115 ESI(Pos)412(M+H)
3116 ESI(Pos)414(M+H)
3117 ESI(Pos)414(M+H)
3118 ESI(Pos)418(M+H)
3119 ESI(Pos)432(M+H)
3120 ESI(Pos)438(M+H)
No. MASS
3121 ESI(Pos)438(M+H)
3122 ESI(Pos)438(M+H)
3123 ESI(Pos)442(M+H)
3124 ESI(Pos)448(M+H)
3125 ESI(Pos)448(M+H)
3126 ESI(Pos)355(M+H)
3127 ESI(Pos)396(M+H)
3128 ESI(Pos)313(M+H)
3129 ESI(Pos)313(M+H)
3130 ESI(Pos)364(M+H)
3131 ESI(Pos)377(M+H)
3132 ESI(Pos)395(M+H)
3133 ESI(Pos)421(M+H)
3134 ESI(Pos)439(M+H)
3135 ESI(Pos)302(M+H)
3136 ESI(Pos)303(M+H)
3137 ESI(Pos)317(M+H)
3138 ESI(Pos)318(M+H)
3139 ESI(Pos)347(M+H)
3140 ESI(Pos)330(M+H)
3141 ESI(Pos)331(M+H)
3142 ESI(Pos)344(M+H)
3143 ESI(Pos)372(M+H)
3144 ESI(Pos)372(M+H)
3145 ESI(Pos)364(M+H)
3146 ESI(Pos)368(M+H)
3147 ESI(Pos)368(M+H)
3148 ESI(Pos)368(M+H)
3149 ESI(Pos)396(M+H)
3150 ESI(Pos)400(M+H)
3151 ESI(Pos)403(M+H)
3152 ESI(Pos)420(M+H)
3153 ESI(Pos)427(M+H)
3154 ESI(Pos)446(M+H)
3155 ESI(Pos)448(M+H)
3156 ESI(Pos)454(M+H)
3157 ESI(Pos)462(M+H)
3158 ESI(Pos)480(M+H)
Table 15
No. MASS
3159 APCI：317(M+H)+
3160 APCI：317(M+H)+
3161 APCI：317(M+H)+
3162 APCI：318(M+H)+
3163 APCI：318(M+H)+
3164 APCI：318(M+H)+
3165 APCI：318(M+H)+
3166 APCI：331(M+H)+
3167 APCI：331(M+H)+
3468 APCI：331(M+H)+
3169 APCI：331(M+H)+
3170 APCI：331(M+H)+
3171 APCI：331(M+H)+
3172 APCI：331(M+H)+
3173 APCI：332(M+H)+
3174 APCI：333(M+H)+
3175 APCI：333(M+H)+
3176 APCI：333(M+H)+
3177 APCI：333(M+H)+
3178 APCI：335(M+H)+
3179 APCI：335(M+H)+
3180 APCI：335(M+H)+
3181 APCI：335(M+H)+
3182 APCI：342(M+H)+
3183 APCI：345(M+H)+
3184 APCI：345(M+H)+
3185 APCI：345(M+H)+
3186 APCI：345(M+H)+
3187 APCI：347(M+H)+
3188 APCI：347(M+H)+
3189 APCI：348(M+H)+
3190 APCI：349(M+H)+
3191 APCI：351(M+H)+
3192 APCI：351(M+H)+
3193 APCI：351(M+H)+
3194 APCI：351(M+H)+
3195 APCI：351(M+H)+
3196 APCI：352(M+H)+
3197 APCI：353(M+H)+
3198 APCI：360(M+H)+
No. MASS
3199 APCI：361(M+H)+
3200 APCI：361(M+H)+
3201 APCI：363(M+H)+
3202 APCI：365(M+H)+
3203 APCI：365(M+H)+
3204 APCI：369(M+H)+
3205 APCI：371(M+H)+
3206 APCI：374(M+H)+
3207 APCI：377(M+H)+
3208 APCI：378(M+H)+
3209 APCI：378(M+H)+
3210 APCI：381(M+H)+
3211 APCI：383(M+H)+
3212 APCI：383(M+H)+
3213 APCI：384(M+H)+
3214 APCI：385(M+H)+
3215 APCI：385(M+H)+
3216 APCI：385(M+H)+
3217 APCI：385(M+H)+
3218 APCI：385(M+H)+
3219 APCI：385(M+H)+
3220 APCI：385(M+H)+
3221 APCI：385(M+H)+
3222 APCI：385(M+H)+
3223 APCI：385(M+H)+
3224 APCI：386(M+H)+
3225 APCI：386(M+H)+
3226 APCI：386(M+H)+
3227 APCI：386(M+H)+
3228 APCI：389(M+H)+
3229 APCI：391(M+H)+
3230 APCI：393(M+H)+
3231 APCI：395(M+H)+
3232 APCI：395(M+H)+
3233 APCI：395(M+H)+
3234 APCI：395(M+H)+
3235 APCI：395(M+H)+
3236 APCI：399(M+H)+
3237 APCI：399(M+H)+
3238 APCI：399(M+H)+
Table 15 (continuing)
No. MASS
3239 APCI：400(M+H)+
3240 APCI：403(M+H)+
3241 APCI：405(M+H)+
3242 APCI：409(M+H)+
3243 APCI：410(M+H)+
3244 APCI：415(M+H)+
3245 APCI：414(M+H)+
3246 APCI：415(M+H)+
3247 APCI：418(M+H)+
3248 APCI：418(M+H)+
3249 APCI：419(M+H)+
3250 ESI：423(M+H)+
3251 APCI：425(M+H)+
3252 APCI：427(M+H)+
3253 APCI：440(M+H)+
3254 APCI：443(M+H)+
3255 APCI：355(M+H)+
3255 APCI：355(M+H)+
3257 APCI：355(M+H)+
3258 APCI：355(M+H)+
3259 APCI：356(M+H)+
3260 APCI：356(M+H)+
3261 APCI：367(M+H)+
3262 APCI：367(M+H)+
3263 APCI：367(M+H)+
3264 APCI：367(M+H)+
3265 APCI：367(M+H)+
3266 APCI：368(M+H)+
3267 APCI：368(M+H)+
3268 APCI：368(M+H)+
3269 APCI：368(M+H)+
3270 APCI：368(M+H)+
3271 APCI：369(M+H)+
3272 APCI：370(M+H)+
3273 APCI：371(M+H)+
3274 APCI：372(M+H)+
3275 APCI：373(M+H)+
3276 APCI：374(M+H)+
3277 APCI：381(M+H)+
3278 APCI：381(M+H)+
No. MASS
3279 APCI：382(M+H)+
3280 APCI：382(M+H)+
3281 APCI：383(M+H)+
3282 APCI：283(M+H)+
3283 APCI：387(M+H)+
3284 APCI：387(M+H)+
3285 APCI：399(M+H)+
3286 APCI：401(M+H)+
3287 APCI：409(M+H)+
3288 APCI：414(M+H)+
3289 APCI：419(M+H)+
3290 APCI：419(M+H)+
3291 APCI：421(M+H)+
3292 APCI：435(M+H)+
3293 APCI：441(M+H)+
3294 APCI：443(M+H)+
3295 APCI：444(M+H)+
3296 APCI：456(M+H)+
3297 APCI：477(M+H)+
3298 APCI：359(M+H)+
3299 APCI：359(M+H)+
3300 APCI：381(M+H)+
3301 APCI：381(M+H)+
3302 APCI：381(M+H)+
3303 APCI：382(M+H)+
3304 APCI：382(M+H)+
3305 APCI：385(M+H)+
3306 APCI：387(M+H)+
3307 APCI：398(M+H)+
3308 APCI：398(M+H)+
3309 APCI：399(M+H)+
3310 APCI：400(M+H)+
3311 APCI：401(M+H)+
3312 APCI：402(M+H)+
3313 APCI：410(M+H)+
3314 APCI：413(M+H)+
3315 APCI：414(M+H)+
3316 APCI：415(M+H)+
3317 APCI：419(M+H)+
3318 APCI：427(M+H)+
Table 15 (continuing)
No. MASS
3319 APCI：431(M+H)+
3320 APCI：435(M+H)+
3321 APCI：444(M+H)+
3322 APCI：449(M+H)+
3323 APCI：449(M+H)+
3324 APCI：451(M+H)+
3325 APCI：451(M+H)+
3326 APCI：459(M+H)+
3327 APCI：483(M+H)+
Test example 1 people CB2 receptors bind inhibition test
With the cDNA sequence of coding people CB2 receptor (Munro etc., Nature, 1993,365,61-65) forward insert the CMV promoter downstream of zooblast with expression vector pTARGET carrier (Promega company).The expression vector that obtains is passed through Lipofectamine (Invitrogen company), and transfection host cell CHO-DHFR (-) obtains CB2 receptor stably express cell.
The film fraction that will make by the Chinese hamster ovary celI of stably express CB2 receptor, reach with test compound [ 3H] CP-55, the Assay buffer of 0.2% bovine serum albumin (50mM Tris-HCl buffer (pH7.4), 2.5mM EDTA, 5mM MgCl are being contained together in 940 (final concentration 0.57nM:Perkin Elmer companies) 2) in, after 2 hours, glass filter (glass filter) GF/C that handles with 0.1% poly-L-Lysine (SIGMA company) filters at 25 ℃ of incubations.After the Assay buffer washing that contains 0.1% bovine serum albumin, obtain radioactivity on the glass filter with liquid scintillation counter.Non-specific binding is at 2.0 μ MCP-55, and there is mensuration down in 940 (Tocris companies), obtain test compound to the bonded 50% inhibition concentration (IC of specificity 50Value).Result of the test is shown in table 16.It is as shown in the table, and test compound shows affinity to the CB2 receptor.
Table 16 people CB2 receptors bind inhibition test
Compound N o. CB2 IC50 (nM)
9 11.3
12 13.3
23 8.9
24 7.5
25 17.4
29 8.6
30 6.6
33 8.2
34 6.6
35 3.4
36 2.2
37 11.3
41 1.4
45 16.5
46 1.2
51 2.6
54 18.7
56 0.8
57 3.8
58 1.8
59 7.2
63 4.9
Compound N o. CB2 IC50 (nM)
67 3.0
70 14.9
71 5.9
73 10.2
74 4.6
76 14.4
77 19.3
78 9.8
79 8.4
80 17.9
81 12.3
85 18.9
86 6.5
88 17.8
89 9.8
90 6.5
91 7.9
92 3.9
93 17.6
94 2.9
96 7.7
97 3.3
Compound N o. CB2 IC50 (nM)
99 6.5
100 7.0
104 1.7
105 1.7
106 6.5
107 0.5
109 1.3
113 1.1
114 1.6
115 0.5
117 5.8
119 18.5
120 7.4
122 8.9
129 7.1
130 8.5
131 5.6
132 15.7
133 7.3
134 6.6
135 11.9
136 11.6
Compound N o. CB2 IC50 (nM)
138 12.0
139 7.4
140 6.1
141 13.9
143 7.4
144 4.3
145 3.9
146 6.6
147 9.6
149 12.2
150 15.0
151 3.2
153 17.8
154 5.9
155 4.3
156 11.4
157 12.1
158 7.1
159 8.4
160 8.5
161 9.7
162 12.0
Table 16 (continuing)
Compound N o. CB2 IC50 (nM)
163 14.9
164 4.1
165 4.3
166 7.2
167 4.6
168 5.4
170 13.8
174 11.7
179 17.8
180 1.0
181 0.8
182 0.3
183 0.5
184 12.0
185 11.0
186 1.7
187 17.0
189 1.5
190 1.0
191 0.7
192 13.2
194 19.1
Compound N o. CB2 IC50 (nM)
195 3.2
196 7.6
197 2.0
198 2.7
200 15.1
201 19.1
206 5.7
209 1.4
210 15.7
211 12.0
215 1.1
216 1.7
217 2.6
218 5.7
219 2.1
220 3.9
221 15.6
222 11.3
223 2.0
224 13.0
225 3.9
226 7.7
Compound N o. CB2 IC50 (nM)
227 8.2
228 0.5
229 1.0
230 1.5
231 3.0
232 0.5
234 0.7
235 3.4
236 2.0
237 13.1
238 4.4
239 2.4
240 3.4
241 1.0
242 4.0
243 0.4
244 3.2
245 0.8
246 0.8
247 0.3
248 5.6
249 0.4
Compound N o. CB2 IC50 (nM)
250 1.1
251 3.4
254 1.4
255 0.6
256 1.1
257 1.3
258 0.6
261 1.0
262 0.6
263 0.6
264 1.0
265 1.0
266 0.8
267 1.1
268 1.1
269 3.6
270 0.7
272 5.0
274 13.2
277 9.0
282 14.5
283 5.9
Table 16 (continuing)
Compound N o. CB2 IC50 (nM)
284 1.2
285 14.2
286 12.7
287 13.5
288 0.2
289 0.5
293 7.0
295 12.3
298 1.5
299 2.8
300 15.0
301 2.0
304 2.3
305 3.7
306 0.5
307 1.0
308 3.6
309 2.1
310 17.3
312 14.0
316 5.3
319 18.6
Compound N o. CB2 IC50 (nM)
320 6.2
321 2.3
322 5.6
323 6.2
324 2.0
325 13.0
326 2.9
327 3.6
328 11.8
330 13.8
332 3.3
335 5.5
336 2.9
337 2.8
338 9.1
341 5.3
344 12.2
345 12.7
346 13.5
348 3.8
349 1.9
350 5.2
Compound N o. CB2 IC50 (nM)
351 2.2
352 2.3
365 3.4
369 1.4
382 17.0
387 13.7
399 6.8
402 15.4
410 7.1
411 8.7
427 5.9
470 10.6
470 10.6
474 4.9
478 3.9
481 3.4
482 1.2
483 8.3
484 2.7
485 1.1
486 5.1
487 9.9
Compound N o. CB2 IC50 (nM)
488 4.0
489 6.0
490 10.0
491 9.3
492 5.0
493 1.9
494 2.1
495 6.3
504 15.4
509 5.9
510 13.2
513 16.9
514 2.6
Test example 2 people CB1 receptors bind inhibition tests
To the combination test of people CB1 receptor and CHO-DHFR (-) cell of test example 1 same making stably express CB1 receptor, carry out the combination experiment, obtain 50% inhibition concentration (IC of test compound 50Value).Result of the test is shown in table 17.It is as shown in the table, and test compound shows affinity to the CB1 receptor.
Table 17 people CB1 receptors bind inhibition test
Compound N o. CB1 IC50 (nM)
56 294
104 327
107 18
115 25
180 395
181 115
182 22
183 138
186 271
189 212
190 53
191 193
206 460
215 61
223 168
228 228
229 263
232 211
235 315
Compound N o. CB1 IC50 (nM)
236 215
237 200
240 168
243 73
245 32
246 319
247 3
249 2
256 102
258 19
261 375
262 435
263 56
264 181
265 100
286 435
288 49
289 136
295 497
Compound N o. CB1 IC50 (nM)
299 28
301 191
304 372
306 68
308 336
309 405
323 362
324 353
327 55
332 98
486 211
487 248
490 291
491 172
492 265
494 279
The receptor-mediated GTP γ of test example 3 people CB1 S is in conjunction with test
Make the Chinese hamster ovary celI of stably express people CB1 receptor according to the method identical, its film fraction with test compound, is being contained the Assay buffer of 0.2% bovine serum albumin [50mM Tris-HCl (pH7.4), 2.5mM EDTA, 5mM MgCl with test example 2 2, 3 μ MGDP (SIGMA company), 30 μ g/ml Saponin (SIGMA company)] in, after 30 minutes, add 0.1nM[at 30 ℃ of incubations 35S] GTP γ S (Perkin Elmer company), 30 ℃ of incubations 30 minutes.Behind the GF/C filtration washing, obtain radioactivity on the glass filter with liquid scintillation counter.Non-specific binding is measured under the non-existent condition of chemical compound, is 100% with the maximum activity value of each test compound, obtains its valid density (EC of 50% 50Value).
The EC of test compound No.247 and No.249 50Value is respectively 33nM and 19nM, and chemical compound of the present invention shows agonism to the CB1 receptor.
The receptor-mediated GTP γ of test example 4 people CB2 S is in conjunction with test
Make the Chinese hamster ovary celI of stably express people CB2 receptor according to the method identical, carry out GTPrS equally with test example 3 and combine test, obtain 50% valid density (EC of the maximum activity of test compound with test example 1 50Value).
The EC of test compound No.9, No.184, No.267 and No.474 50Value is respectively 23.7nM, 9.8nM, 0.4nM and 2.3nM, and chemical compound of the present invention shows agonism to the CB2 receptor.
The test of test example 5 mice acetic acid twistings
This test is carried out (Gen Pharmacol.24 (1): 105-110 (1993)) according to the method for Futaki N etc.Using Jcl:ICR is male mice (5 age in week), oral giving and outstanding turbid test compound in 5% gumwater.After the test compound administration 1 hour, intraperitoneal is given and 0.9% aqueous acetic acid, and it measures the number of times of the abdominal part stretching (pain behavior) in 10 minutes after 5 minutes.Matched group is only oral to be given and 5% gumwater, calculates pain behavior suppression ratio (%) with following formula.
[several 1]
Figure A20058003900503141
The 30mg/kg of test compound No.59, No.247, No.267, No.411, No.474 and No.510, the suppression ratio of oral administration are respectively 44.8%, 93.0%, 59.9%, 49.0%, 61.9% and 19.6%, compound exhibits analgesic activity of the present invention.
Test example 6 rat nerves are because of the test of property pain
Using SD:IGS is male rat (5 age in week), according to the method (SeltzerZ of Seltzer etc.; Pain.43 (2): 205-218 (1990)), make nerve with the sciatic nerve part ligation of huckle because of the property pain model, (touching stimulates the inspection nylon fiber with von Frey filament; North Coast Medical Inc.) touches the vola that stimulates the damage side, measures the variation of pain threshold (the fiber load-carrying gram number when animal reacts to touching stimulation).Test compound is outstanding turbid in 5% gumwater, and with the consumption oral administration of 0mg/kg, 3mg/kg, 10mg/kg and 30mg/kg, it measures pain threshold (g) after 1 hour.
The oral administration of test compound No.184 rises pain threshold with consumption, has improved hyperalgesia (Fig. 1).
The test of test example 7 Mice Auricle edema
Using Balb/c is male mice (5 age in week), test compound is dissolved in acetone, at the inboard coating of auricle 20 μ L.The test compound coating is after 10 minutes, and coating contains acetone (the 20 μ L) solution of PMA (phorbol 12-myristate 13-acetate) 0.8 μ g, and it measured the auricle plumpness with dial sickness gauge after 5 hours.Matched group is only disposed with acetone, calculates auricle edema suppression ratio (%) with following formula.
[several 2]
Figure A20058003900503151
Test compound No.184, No.267 and No.474 bring medicine 1mg in Mice Auricle one, show 65%, 84% and 37% suppression ratio respectively, the swollen effect of compound exhibits anti-floating of the present invention.
Industrial applicibility
The invention provides the group with imine moiety with Cannabined receptor agonism. Group with imine moiety of the present invention has the Cannabined receptor agonism, and is useful as therapeutic agent or the prophylactic of pain, autoimmune disease.
Description of drawings
Fig. 1 represents to test the rat nerve of example 6 because of property pain result of the test.

Claims (56)

1. the Cannabined receptor excitomotor that is effective ingredient with group with imine moiety or its officinal salt of formula (I) expression.
Figure A2005800390050002C1
[in the formula, A represents any one ring (in the formula, X represents oxygen atom or sulphur atom, X ' expression CH or nitrogen-atoms) of following various expression,
Figure A2005800390050002C2
R 1Expression
Hydrogen atom;
Halogen atom;
Can be by the C of " halogen atom substituted aryl " replacement 1-10Alkyl;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression; Perhaps
C can be selected from 1-6Alkyl, C 1-6The aryl that 1～3 group of haloalkyl and halogen atom replaces,
R 2And R 3Expression respectively
Hydrogen atom;
Halogen atom;
C 1-6Alkyl;
C 1-6Haloalkyl; Perhaps
C can be selected from 1-6Alkyl, C 1-6The aryl that 1～3 group of haloalkyl and halogen atom replaces,
R 4Expression
C 1-10Alkyl;
C 1-6Haloalkyl;
By C 3-10Cycloalkyl, C 1-6Alkoxyl, hydroxyl, amino, phthaloyl imino, cyano group, arylthio, C 2-6Alkoxy carbonyl, carboxyl, formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression or can be by " C 1-6Haloalkyl, C 2-6Alkoxy carbonyl, carboxyl or N-piperidino carbamoyl " C that replaces of the aryl that replaces 1-10Alkyl or C 2-6Thiazolinyl;
C 2-6Haloalkenyl group;
C 2-6Alkynyl;
1,1-dioxo tetrahydro-thienyl;
Or aryl,
R 5Expression
Hydrogen atom;
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, C 1-6Haloalkyl, can be by " C 1-6Alkoxyl or aryl " C that replaces 1-6Alkoxyl, can be by 1～2 C 1-6The C that alkyl replaces 3-10Cycloalkyloxy, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl, C 1-6Halogenated alkoxy, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, phthaloyl imino, C 1-6Alkanoyloxy, aralkoxy, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group in the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkyl, C 1-6Alkoxyl, C 2-6Alkoxy carbonyl, C 1-6Haloalkyl or C 1-6The aryloxy group that halogenated alkoxy replaces;
Aralkoxy;
The group of formula (II) expression,
Figure A2005800390050004C1
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
Fluorenyl;
Phthaloyl imino;
2-oxo-pyrrolidine base;
The group of formula (III) expression;
Figure A2005800390050005C1
(in the formula, n represents 0 or 1.)
The perhaps group of formula (IV) expression;
Figure A2005800390050005C2
(in the formula, Y represents-(CH 2) p-,-CO-CH 2-CH 2-,-CO-CH 2-CH 2-CH 2-,-O-CH 2-CH 2-,-O-CH 2-CH=CH-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer)
R 55Expression
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or the aryloxy group that can be replaced by halogen atom; Or formula-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Can be by C 1-6The aryl sulfonyl that alkyl or halogen atom replace;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl, cyano group and nitro replaces;
Can be by C 1-6Alkyl or C 1-6The heterocyclic group that haloalkyl replaces;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 63) R 73(in the formula, R 63And R 73Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Hydroxy alkyl, C 1-6Alkoxy C 1-6Alkyl, aryl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl, benzoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 1-6Alkanoyloxy;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 2-6The alkyl halide acyl group;
Carboxyl;
C 2-6Alkoxy carbonyl;
The C that can be replaced by aryl 2-6Cyclic amino;
Formula-CON (R 64) R 74(in the formula, R 64And R 74Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkoxy C 1-6Alkyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-SO 2N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
C 1-6Alkyl sulphinyl;
The C that can be replaced by halogen atom 1-6Alkyl sulphonyl; Perhaps
The aryl sulfonyl that can be replaced by halogen atom,
R 56Expression
Hydrogen atom;
Halogen atom;
Can by: can be by " C 1-6Alkyl or halogen atom " C that replaces of the aryl, pyridine radicals, thienyl or the heterocyclic group that replace 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl;
C 1-10Alkoxyl;
C 2-6Thiazolinyl;
C can be selected from 1-6Alkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
C 1-6Alkanoyl;
C 1-6Alkyl sulphinyl;
C 1-6Alkyl sulphonyl;
The aryl sulfonyl that can be replaced by halogen atom;
Hydroxyl;
Cyano group; Perhaps
Nitro,
R 57Expression
Hydrogen atom;
Can be by the C of " pyridine radicals or thienyl " replacement 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl;
Halogen atom;
C 2-6Thiazolinyl;
The aryl that can be replaced by halogen atom;
C 1-10Alkoxyl;
C 1-6Alkanoyl; Perhaps
C 1-6Alkyl sulphinyl,
M represents 1～3 integer }
A and b represent 0 or 1 respectively,
W represents-CO-,-CO-CO-,-CO-NH-,-CS-NH-or-SO 2-.]
2. Cannabined receptor excitomotor as claimed in claim 1,
With R 1Be hydrogen atom;
Halogen atom;
Can be by the C of " halogen atom substituted aryl " replacement 1-10Alkyl;
C 3-10Cycloalkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression; Perhaps
C can be selected from 1-6Alkyl, C 1-6The aryl that 1～3 group of haloalkyl and halogen atom replaces,
R 4For
C 1-10Alkyl;
C 1-6Haloalkyl;
By C 3-10Cycloalkyl, C 1-6Alkoxyl, hydroxyl, amino, phthaloyl imino, cyano group, arylthio, C 2-6Alkoxy carbonyl, carboxyl, formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression or can be by " C 1-6Haloalkyl, C 2-6Alkoxy carbonyl, carboxyl or N-piperidino carbamoyl " C that replaces of the aryl that replaces 1-10Alkyl;
The C that can be replaced by aryl 2-6Thiazolinyl;
C 2-6Haloalkenyl group;
C 2-6Alkynyl;
1,1-dioxo tetrahydro-thienyl; Perhaps
Aryl,
R 5For
C 1-10Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, C 1-6Haloalkyl, can be by " C 1-6Alkoxyl or aryl " C that replaces 1-6Alkoxyl, can be by 1～2 C 1-6The C that alkyl replaces 3-10Cycloalkyloxy, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl, C 1-6Halogenated alkoxy, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, phthaloyl imino, C 1-6Alkanoyloxy, aralkoxy, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group of the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkyl, C 1-6Alkoxyl, C 2-6Alkoxy carbonyl, C 1-6Haloalkyl or C 1-6The aryloxy group that halogenated alkoxy replaces; Perhaps
The group of formula (II) expression, B is C 3-10Cycloalkyl, aryl or heterocyclic group,
R 55And R 56Be respectively
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Can be by C 1-6The aryl sulfonyl that alkyl or halogen atom replace;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl, cyano group and nitro replaces;
Can be by C 1-6Alkyl or C 1-6The heterocyclic group that haloalkyl replaces;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 63) R 73(in the formula, R 63And R 73Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Hydroxy alkyl, C 1-6Alkoxy C 1-6Alkyl, aryl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl, benzoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 1-6Alkanoyloxy;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 2-6The alkyl halide acyl group;
Carboxyl;
C 2-6Alkoxy carbonyl;
Formula-CON (R 64) R 74(in the formula, R 64And R 74Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkoxy C 1-6Alkyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 57Be hydrogen atom, C 1-10Alkyl, C 1-6Haloalkyl, halogen atom or C 1-10The group with imine moiety of alkoxyl or its officinal salt are effective ingredient.
3. with the group with imine moiety of formula (I-1) expression or its officinal salt Cannabined receptor excitomotor as effective ingredient,
Figure A2005800390050011C1
[in the formula, A 1Any one ring (in the formula, X represents oxygen atom or sulphur atom) of representing following various expression,
R 11Expression
Hydrogen atom;
Halogen atom;
C 1-6Alkyl;
C 2-6Thiazolinyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl; Perhaps
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 21And R 31Expression respectively
Hydrogen atom;
Halogen atom; Perhaps
C 1-6Alkyl,
R 41Expression
Can be by halogen atom, C 3-10Cycloalkyl, aryl or C 1-6The C that alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl,
R 51Expression
C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl and halogen atom " the aryl that replaces of 1～5 group or the C that replaces of 1～3 group of aryloxy group and heterocyclic group 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-1) expression,
Figure A2005800390050012C1
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
Fluorenyl; Perhaps
The group of formula (IV-1) expression,
Figure A2005800390050012C2
(in the formula, Y 1Expression-(CH 2) p-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer)
R 551And R 561Expression respectively
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 634) R 734(in the formula, R 634And R 734Represent hydrogen atom, C respectively 1-6Alkyl, aryl or C 1-6Alkanoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group;
C 1-6Alkyl sulphonyl; Perhaps
The aryl sulfonyl that can be replaced by halogen atom,
R 571Expression
Hydrogen atom;
C 1-10Alkyl;
C 1-10Alkoxyl; Perhaps
Halogen atom,
M represents 1～3 integer }, a and b represent 0 or 1 respectively, W represents CO or SO 2]
4. as claimed in claim 3 is the Cannabined receptor excitomotor of effective ingredient with group with imine moiety or its officinal salt,
R 51For being selected from halogen atom, C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl and halogen atom " C that replaces of 1～3 group of the aryl, thienyl and the aryloxy group that replace 1-10Alkyl or C 2-6Thiazolinyl, the perhaps group of formula (II-1) expression,
R 551For
Hydrogen atom;
Halogen atom;
Can be by C that aryl, heterocyclic group or the aryloxy group that can be replaced by halogen atom replaces 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C can be selected from 1-6Alkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 631) R 731(in the formula, R 631And R 731Represent hydrogen atom, C respectively 1-6Alkyl, aryl or C 1-6Alkanoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Cyano group;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group; Perhaps
C 1-6Alkyl sulphonyl,
R 561For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-10Alkoxyl,
R 571For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl.
As claim 3 or 4 described be the Cannabined receptor excitomotor of effective ingredient with group with imine moiety or its officinal salt,
Wherein, A 1The ring of representing for following formula.
6. as claimed in claim 5 is the Cannabined receptor excitomotor of effective ingredient with group with imine moiety or its officinal salt,
R 51For can be by C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl and halogen atom " C that replaces of the aryl, thienyl or the aryloxy group that replace 1-10The group of alkyl or formula (II-1) expression,
B is C 3-10Cycloalkyl, aryl or heterocyclic group,
R 551For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C can be selected from 1-6The aryl that 1～3 group of alkyl and halogen atom replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
Aryloxy group;
Morpholinyl;
Arylamino;
Cyano group;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group; Perhaps
C 1-6Alkyl sulphonyl,
R 561For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-10Alkoxyl,
R 571For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl.
7. as claimed in claim 6 is the Cannabined receptor excitomotor of effective ingredient with group with imine moiety or its officinal salt,
R 51Be the group of formula (II-1) expression,
B is a phenyl,
R 551For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
Aryl;
Aryloxy group;
Morpholinyl;
Arylamino;
Cyano group;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group;
Or C 1-6Alkyl sulphonyl,
R 561For
Hydrogen atom;
Halogen atom;
C 1-6Haloalkyl;
Or C 1-6Alkoxyl,
R 571For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl (wherein, R 551, R 571And R 41During for alkyl, R 551And R 571Carbon number be 1～6, R 41Carbon number be 2～10), m is 1.
8. as each described Cannabined receptor excitomotor in the claim 1～7, be cannabinoid 1 receptor excitomotor or cannabinoid 2 receptor excitomotors.
9. as each described Cannabined receptor excitomotor in the claim 1～7, be treatment of pain agent or preventive.
10. as each described Cannabined receptor excitomotor in the claim 1～7, be the therapeutic agent or the preventive of autoimmune disease.
11. group with imine moiety or its officinal salt of formula (I-1) expression.
Figure A2005800390050017C1
[in the formula, A 1Any one ring (in the formula, X represents oxygen atom or sulphur atom) of representing following various expression,
Figure A2005800390050017C2
R 11Expression
Hydrogen atom;
Halogen atom;
C 1-6Alkyl;
C 2-6Thiazolinyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl; Perhaps
Formula-N (R 6) R 7(in the formula, R 6And R 7Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 21And R 31Expression respectively
Hydrogen atom;
Halogen atom; Perhaps
C 1-6Alkyl,
R 41Expression
Can be by halogen atom, C 3-10Cycloalkyl, aryl or C 1-6The C that alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl,
R 51Expression
C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, " C can be selected from 1-6Alkyl, C 1-6Alkoxyl, C 1-6Haloalkyl and halogen atom " the aryl that replaces of 1～5 group or the C that replaces of 1～3 group of aryloxy group and heterocyclic group 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-1) expression,
Figure A2005800390050018C1
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
Fluorenyl; Perhaps
The group of formula (IV-1) expression,
Figure A2005800390050019C1
(in the formula, Y 1Expression-(CH 2) p-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer)
R 551And R 561Expression respectively
Hydrogen atom;
Halogen atom;
Can be by aryl, heterocyclic group or aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 634) R 734(in the formula, R 634And R 734Represent hydrogen atom, C respectively 1-6Alkyl, aryl or C 1-6Alkanoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group;
C 1-6Alkyl sulphonyl; Perhaps
The aryl sulfonyl that can be replaced by halogen atom,
R 571Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl,
M represents 1～3 integer }, a and b represent 0 or 1 respectively, W represents CO or SO 2]
12. group with imine moiety as claimed in claim 11 or its officinal salt,
R 51For being selected from halogen atom, C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl and halogen atom " C that replaces of 1～3 group of the aryl, thienyl and the aryloxy group that replace 1-10Alkyl or C 2-6Thiazolinyl, the perhaps group of formula (II-1) expression,
R 551For
Hydrogen atom;
Halogen atom;
Can be by C that aryl, heterocyclic group or the aryloxy group that can be replaced by halogen atom replaces 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C can be selected from 1-6Alkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 631) R 731(in the formula, R 631And R 731Represent hydrogen atom, C respectively 1-6Alkyl, aryl or C 1-6Alkanoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Cyano group;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group; Perhaps
C 1-6Alkyl sulphonyl,
R 561For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-10Alkoxyl,
R 571For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl.
13. as claim 11 or 12 described group with imine moiety or its officinal salt, W is-CO-.
14. group with imine moiety as claimed in claim 13 or its officinal salt, R 41Be C 1-6The C that alkoxyl or aryl replace 1-10Alkyl, R 551Be C 1-6Haloalkyl, R 564Be halogen atom.
15. group with imine moiety as claimed in claim 13 or its officinal salt, R 41Be C 3-10Cycloalkyl or C 1-6The C that alkoxyl replaces 1-10Alkyl.
16. as claim 14 or 15 described group with imine moiety or its officinal salt, A 1Be 1, the 2-dihydropyridine ring.
17. group with imine moiety as claimed in claim 16 or its officinal salt, R 51For can be by C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl and halogen atom " C that replaces of the aryl, thienyl or the aryloxy group that replace 1-10The group of alkyl or formula (II-1) expression,
B is C 3-10Cycloalkyl, aryl or heterocyclic group,
R 551For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
C can be selected from 1-6The aryl that 1～3 group of alkyl and halogen atom replaces;
Can be by C 1-6The heterocyclic group that alkyl replaces;
Aryloxy group;
Morpholinyl;
Arylamino;
Cyano group;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group; Perhaps
C 1-6Alkyl sulphonyl,
R 561For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-10Alkoxyl,
R 571For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl.
18. group with imine moiety as claimed in claim 17 or its officinal salt,
R 51Be the group of formula (II-1) expression,
B is a phenyl,
R 551For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl;
C 1-6Halogenated alkoxy;
C 3-10Cycloalkyl;
Aryl;
Aryloxy group;
Morpholinyl;
Arylamino;
Cyano group;
C 1-6Alkanoyl;
C 2-6The alkyl halide acyl group;
Or C 1-6Alkyl sulphonyl,
R 561For
Hydrogen atom;
Halogen atom;
C 1-6Haloalkyl;
Or C 1-6Alkoxyl,
R 571For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Or
C 1-10Alkoxyl, m are 1.
19. group with imine moiety as claimed in claim 18 or its officinal salt, R 41Be C 3-10The C of cycloalkyl substituted 1-10Alkyl.
20. group with imine moiety as claimed in claim 19 or its officinal salt, R 51For being selected from halogen atom, C 1-10Alkyl, C 1-6Haloalkyl, C 1-10Alkoxyl, cyano group and C 1-6The phenyl that 1～3 group of halogenated alkoxy replaces.
21. as each described group with imine moiety or its officinal salt in the claim 13～20, in formula (I-1), the spatial configuration of two keys that the carbon atom of group shown in the＞C=N-CO-and nitrogen-atoms form is (Z) configuration.
22. with the group with imine moiety of formula (I-2) expression or its officinal salt Cannabined receptor excitomotor as effective ingredient.
Figure A2005800390050024C1
[in the formula, R 12And R 22Expression respectively
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Can be by the aryl of 1～3 halogen atom replacement; Perhaps
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression, perhaps represent R 11And R 22Connecting together with adjacent carbon atom, form can be by C 1-6The group of phenyl ring, pyridine ring or cyclohexene ring that alkyl or halogen atom replace,
R 42Expression
Can be by halogen atom, cyano group, carboxyl, C 2-6Alkoxy carbonyl, C 3-10Cycloalkyl, can be by " C 1-6Haloalkyl, C 1-6Halogenated alkoxy, C 1-6Halogenated alkylthio, carboxyl, C 2-6Alkoxy carbonyl or piperidino carbamoyl " aryl, arylthio, the C that replace 1-6Alkoxyl or formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl or C 2-6Thiazolinyl; Perhaps
C 2-6Alkynyl,
R 52Expression
Hydrogen atom;
C 1-6Alkoxyl;
C 1-6Haloalkyl;
Can be selected from halogen atom, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, can be by " C 1-6Alkoxyl or aryl " C that replaces 1-6Alkoxyl, can be by C 1-6The C that alkyl replaces 3-10Cycloalkyloxy, " C can be selected from 1-6Alkyl, C 1-6Haloalkyl, C 1-6Alkoxyl, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, phthaloyl imino, C 1-6Alkanoyloxy, aralkoxy, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group of the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkyl, C 1-6Alkoxyl, C 2-6Alkoxy carbonyl or C 1-6The aryloxy group that haloalkyl replaces;
Aralkoxy;
The group of formula (II-2) expression,
Figure A2005800390050025C1
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
Fluorenyl;
2-oxo-pyrrolidine base;
The group of formula (III) expression;
Figure A2005800390050026C1
(in the formula, n represents 0 or 1)
The perhaps group of formula (IV-2) expression,
Figure A2005800390050026C2
(in the formula, Y 2Expression-(CH 2) p-,-CO-CH 2-CH 2-,-O-CH 2-CH=CH-or-O-(CH 2) q-O-, p represents 2～4 integer, q represents 1～3 integer),
R 552Expression
Hydrogen atom;
Halogen atom;
Can be by aryl, aryloxy group or formula-N (R that can be replaced by halogen atom 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Can be by C 1-6The arylthio that alkyl or halogen atom replace;
Can be by C 1-6The aryl sulfonyl that alkyl or halogen atom replace;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 3-10Cycloalkyl;
C 2-6Thiazolinyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6Alkyl, C 1-6Haloalkyl, halogen atom, C 1-6The aryl that 1～3 group of alkoxyl and nitro replaces;
Can be by C 1-6Alkyl or C 1-6The heterocyclic group that haloalkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 63) R 73(in the formula, R 63And R 73Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Hydroxy alkyl, C 1-6Alkoxy C 1-6Alkyl, aryl, C 1-6Alkanoyl or benzoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
Carboxyl;
C 2-6Alkoxy carbonyl;
Can be by the C of aralkyl or aryl replacement 2-6Cyclic amino;
Formula-CON (R 64) R 74(in the formula, R 64And R 74Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkoxy C 1-6Alkyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Formula-SO 2N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
The C that can be replaced by halogen atom 1-6Alkyl sulphonyl;
The aryl sulfonyl that can be replaced by halogen atom; Perhaps
2-oxa--3-oxo bicyclo-[2.2.1] heptyl,
R 562Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-6Alkoxyl,
R 572Expression
Hydrogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
Halogen atom; Perhaps
C 1-6Alkoxyl,
M represents 1～3 integer }, X represents oxygen atom or sulphur atom, W represents CO or SO 2]
23. as claimed in claim 22 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient, X is a sulphur atom.
24. it is as claimed in claim 23 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 12Be hydrogen atom, halogen atom, C 1-10Alkyl, carboxyl, C 2-6Alkoxy carbonyl, formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group or the aryl of expression,
R 22Be hydrogen atom, C 1-10Alkyl, C 1-6Haloalkyl or aryl perhaps are R 11And R 22Connecting together with adjacent carbon atom, form can be by C 1-6The group of phenyl ring, pyridine ring or cyclohexene basic ring that alkyl or halogen atom replace.
25. it is as claimed in claim 24 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 42For can be by halogen atom, cyano group, carboxyl, C 2-6Alkoxy carbonyl, C 3-10Cycloalkyl, can be by " C 1-6Halogenated alkylthio, carboxyl or C 2-6Alkoxy carbonyl " aryl, arylthio, the C that replace 1-6Alkoxyl or formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl or C 2-6Thiazolinyl; Perhaps
C 2-6Alkynyl,
R 52For
C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, C 1-6Alkoxyl, " C can be selected from 1-6Alkyl, C 1-6Haloalkyl, C 1-6Alkoxyl, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group in the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkoxyl, C 2-6Alkoxy carbonyl or C 1-6The aryloxy group that haloalkyl replaces; Perhaps
The group of formula (II) expression,
B is
C 3-10Cycloalkyl;
Aryl; Perhaps
Heterocyclic group,
R 552For
Hydrogen atom;
Halogen atom;
Can be by aryl or formula-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Arylthio;
The aryl sulfonyl that can be replaced by halogen atom;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6The aryl that 1～3 group of haloalkyl, halogen atom and nitro replaces;
Can be by C 1-6The heterocyclic group that haloalkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 63) R 73(in the formula, R 63And R 73Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Hydroxy alkyl, C 1-6Alkoxy C 1-6Alkyl or benzoyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Hydroxyl;
Cyano group;
Nitro;
Carboxyl;
C 2-6Alkoxy carbonyl;
Formula-CON (R 64) R 74(in the formula, R 64And R 74Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkoxy C 1-6Alkyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 562For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-10Alkoxyl,
R 572For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Alkoxyl.
26. it is as claimed in claim 25 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 52Be the group of formula (II-2) expression, B is phenyl or pyridine radicals, R 552For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Or
C 1-10Alkoxyl,
R 562For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Alkoxyl,
R 572For
Hydrogen atom;
Halogen atom; Perhaps
C 1-6Alkoxyl.
27. it is as claimed in claim 26 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 42For can be by halogen atom, cyano group, carboxyl, C 2-6Alkoxy carbonyl, C 3-10Cycloalkyl, can be by " C 1-6Halogenated alkylthio, carboxyl or C 2-6Alkoxy carbonyl " aryl, arylthio, the C that replace 1-6Alkoxyl or formula-CON (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl.
28., be cannabinoid 1 receptor excitomotor or cannabinoid 2 receptor excitomotors as each described Cannabined receptor excitomotor in the claim 22～27.
29., be treatment of pain agent or preventive as each described Cannabined receptor excitomotor in the claim 22～27.
30., be the therapeutic agent or the preventive of autoimmune disease as each described Cannabined receptor excitomotor in the claim 22～27.
31. a group with imine moiety or its officinal salt, in following formula (I-2),
Figure A2005800390050031C1
W is CO,
R 12For
Halogen atom;
C 1-6Alkyl;
C 1-6Haloalkyl;
C 1-6Alkoxyl;
Carboxyl;
C 2-6Alkoxy carbonyl;
Hydroxyl C 1-6Alkyl;
Can be by the aryl of 1～3 halogen atom replacement; Perhaps
Formula-CON (R 61) R 71(in the formula, R 61And R 71Represent hydrogen atom or the C that can be replaced by cyclic amino respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression,
R 22For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Or
Aryl perhaps is R 12And R 22Connecting together with adjacent carbon atom, form can be by C 1-6The group of phenyl ring, pyridine ring or cyclohexene ring that alkyl or halogen atom replace,
R 42Be C 3-10Cycloalkyl or C 1-6The C that alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl,
X and R 52Identical with above-mentioned implication.
32. group with imine moiety as claimed in claim 31 or its officinal salt, X are sulphur atom.
33. group with imine moiety as claimed in claim 32 or its officinal salt, R 12Be halogen atom or C 1-10Alkyl, R 22Be C 1-10Alkyl or C 1-6Haloalkyl.
34. group with imine moiety as claimed in claim 33 or its officinal salt,
R 52For
C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, C 1-6Alkoxyl, " C can be selected from 1-6Alkyl, C 1-6Haloalkyl, C 1-6Alkoxyl, aralkoxy, nitro and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkylthio group, arylthio and-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of 1～3 group in the group of expression 1-10Alkyl or C 2-6Thiazolinyl;
Can be by C 1-6Alkoxyl, C 2-6Alkoxy carbonyl or C 1-6The aryloxy group that haloalkyl replaces; Perhaps
The group of formula (II-2) expression,
B is
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group,
R 552For
Hydrogen atom;
Halogen atom;
Can be by aryl or formula-N (R 62) R 72(in the formula, R 62And R 72Represent hydrogen atom or C respectively 1-6Alkyl, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) C that replaces of the group of expression 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 1-6Alkyl sulphonyl;
Arylthio;
The aryl sulfonyl that can be replaced by halogen atom;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
C 1-6Alkoxy C 1-6Alkoxyl;
C can be selected from 1-6The aryl that 1～3 group of haloalkyl, halogen atom and nitro replaces;
Can be by C 1-6The heterocyclic group that haloalkyl replaces;
The aryloxy group that can be replaced by halogen atom;
Hydroxyl;
Cyano group;
Nitro;
Carboxyl; Perhaps
C 2-6Alkoxy carbonyl,
R 562For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-10Alkoxyl,
R 572For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl.
35. group with imine moiety as claimed in claim 34 or its officinal salt,
R 52Be the group of formula (II-2) expression, B is phenyl or pyridine radicals, R 552For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl; Perhaps
C 1-6Halogenated alkoxy,
R 562For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-10Alkoxyl,
R 572For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-10Alkoxyl.
36. as each described group with imine moiety or its officinal salt in the claim 31～35, formula (I-2)＞C=N-CO-shown in the spatial configuration of two keys of group be (Z) configuration.
37. with the group with imine moiety of formula (I-3) expression or its officinal salt Cannabined receptor excitomotor as effective ingredient.
Figure A2005800390050034C1
[in the formula, dotted line is represented one of any two keys that are,
X 3Expression C (R 13), S or O,
R 13, R 23And R 33Expression respectively
Hydrogen atom;
The C that can be replaced by the halogen atom substituted aryl 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl; Or
Can be by the aryl or aralkyl of 1～3 halogen atom replacement, perhaps X 3Be C (R 13) time, R 13With R 23Expression-CH connects together 2-S-CH 2Group (wherein, the X of-expression 3During for S or O, R 33Be not substituted),
R 43Expression
1,1-dioxo tetrahydro-thienyl;
C can be selected from 3-10Cycloalkyl, C 1-6Haloalkyl and C 1-6The C that the group of alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl; Perhaps aryl,
R 53Expression
Hydrogen atom;
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, " C can be selected from 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkanoyloxy, aralkoxy and C 1-6The C that 1～3 group in the alkylthio group replaces 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-3) expression,
Figure A2005800390050035C1
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
The group of formula (III) expression;
Figure A2005800390050036C1
(in the formula, n represents 0 or 1.)
The perhaps group of formula (IV-3) expression,
Figure A2005800390050036C2
(in the formula, Y 3Expression-O-CH 2-CH=CH-or-O-(CH 2) q-O-, q represents 1～3 integer)
R 553Expression
Hydrogen atom;
Halogen atom;
Aryl;
C 1-10Alkyl;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
Can be by the aryl of 1～3 halogen atom or cyano group replacement;
Heterocyclic group;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 633) R 733(in the formula, R 633And R 733Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Cyano group;
Nitro;
C 2-6Alkoxy carbonyl;
R 563Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Haloalkyl,
R 573Expression
Hydrogen atom;
C 1-10Alkyl;
Halogen atom; Perhaps
C 1-10Alkoxyl,
M represents 1～3 integer }, W represents-CO-,-CO-CO-,-CO-NH-,-CS-NH-or-SO 2-.]
38. it is as claimed in claim 37 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 13Be hydrogen atom or phenyl, R 23And R 33Be respectively C 1-6Alkyl, C 1-6Haloalkyl or C 3-10Cycloalkyl,
R 43For
C can be selected from 3-10Cycloalkyl, C 1-6Haloalkyl and C 1-6The C that the group of alkoxyl replaces 1-10Alkyl,
R 53For
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, " C can be selected from 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkanoyloxy, aralkoxy and C 1-6The C that 1～3 group in the alkylthio group replaces 1-10Alkyl or C 2-6Thiazolinyl; Perhaps
The group of formula (II-3) expression,
B is the group of aryl, furyl, thienyl, pyrazolyl, different  azoles base, pyridine radicals, formula (III) expression or the group of formula (IV-3) expression.
39. as claimed in claim 38 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient, W is-CO-.
40. it is as claimed in claim 39 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
X 3Be C (R 13),
R 53For
C 1-10Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl and can be selected from " C 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group in the C that replaces of 1～3 group 1-10Alkyl; Perhaps
The group of formula (II-3) expression, B is a phenyl.
41. it is as claimed in claim 40 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 553For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Halogenated alkoxy;
Can be by the aryl of 1～3 halogen atom replacement;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 633) R 733(in the formula, R 633And R 733Represent hydrogen atom or C respectively 1-6Alkyl) Biao Shi group;
Cyano group;
Nitro; Perhaps
C 2-6Alkoxy carbonyl,
R 563For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Alkoxyl; Perhaps
C 1-6Haloalkyl,
R 573For
Hydrogen atom;
C 1-10Alkyl;
Halogen atom; Perhaps
C 1-10Alkoxyl.
42. it is as claimed in claim 39 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
X 3Be sulphur atom, R 53Be the group of formula (II-3) expression, B is a phenyl.
43. it is as claimed in claim 42 with group with imine moiety or its officinal salt Cannabined receptor excitomotor as effective ingredient,
R 553For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl; Perhaps
C 1-10Alkoxyl,
R 563For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl;
C 1-6Alkoxyl; Perhaps
C 1-6Haloalkyl,
R 573Be hydrogen atom.
44. as claim 41 or 43 described with group with imine moiety or its officinal salt Cannabined receptor excitomotor, R as effective ingredient 43Be C 3-10The C of cycloalkyl substituted 1-10Alkyl.
45., be cannabinoid 1 receptor excitomotor or cannabinoid 2 receptor excitomotors as each described Cannabined receptor excitomotor in the claim 37～44.
46., be treatment of pain agent or preventive as each described Cannabined receptor excitomotor in the claim 37～44.
47., be the therapeutic agent or the preventive of autoimmune disease as each described Cannabined receptor excitomotor in the claim 37～44.
48. group with imine moiety or its officinal salt of formula (I-3) expression.
Figure A2005800390050040C1
[in the formula, dotted line one of represents arbitrarily to be two keys,
X 3Expression C (R 13), S or O,
R 13, R 23And R 33Expression respectively
Hydrogen atom;
The C that can be replaced by the halogen atom substituted aryl 1-10Alkyl;
C 1-6Haloalkyl;
C 3-10Cycloalkyl; Or
Can be by the aryl or aralkyl of 1～3 halogen atom replacement, perhaps X 3Be C (R 13) time, R 13With R 23Expression-CH connects together 2-S-CH 2Group (wherein, the X of-expression 3During for S or O, R 33Be not substituted),
R 43Expression
1,1-dioxo tetrahydro-thienyl;
C can be selected from 3-10Cycloalkyl, C 1-6Haloalkyl and C 1-6The C that the group of alkoxyl replaces 1-10Alkyl or C 2-6Thiazolinyl; Perhaps aryl,
R 53Expression
Hydrogen atom;
C 1-10Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, " C can be selected from 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkanoyloxy, aralkoxy and C 1-6The C that 1～3 group in the alkylthio group replaces 1-10Alkyl or C 2-6Thiazolinyl;
The group of formula (II-3) expression,
Figure A2005800390050041C1
{ in the formula, B represents
C 3-10Cycloalkyl;
Aryl;
Heterocyclic group;
C 2-6Cyclic amino;
The group of formula (III) expression;
Figure A2005800390050041C2
(in the formula, n represents 0 or 1)
The perhaps group of formula (IV-3) expression,
Figure A2005800390050042C1
(in the formula, Y 3Expression-O-CH 2-CH=CH-or-O-(CH 2) q-O-, q represents 1～3 integer)
R 553Expression
Hydrogen atom;
Halogen atom;
Aryl;
C 1-10Alkyl;
C 1-6Alkanoyloxy C 1-6Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Alkylthio group;
C 2-6Alkene oxygen base;
C 2-6Alkenylthio group;
C 1-6Halogenated alkoxy;
C 1-6Halogenated alkylthio;
Can be by the aryl of 1～3 halogen atom or cyano group replacement;
Heterocyclic group;
Can be by halogen atom or C 1-6Aryloxy group or arylthio that alkyl replaces;
Formula-N (R 633) R 733(in the formula, R 633And R 733Represent hydrogen atom, C respectively 1-6Alkyl, C 1-6Alkanoyl, two C 1-6Alkyl amino C 2-6Alkanoyl or can be by C 1-6The heterocyclic group that alkyl replaces, perhaps expression connects together with adjacent nitrogen-atoms and forms the group of cyclic amino) group of expression;
Cyano group;
Nitro;
C 2-6Alkoxy carbonyl;
R 563Expression
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Haloalkyl,
R 573Expression
Hydrogen atom;
C 1-10Alkyl;
Halogen atom; Perhaps
C 1-10Alkoxyl,
M represents 1～3 integer }, W represents-CO-,-CO-CO-,-CO-NH-,-CS-NH-or-SO 2-.]
49. group with imine moiety as claimed in claim 48 or its officinal salt, R 13Be hydrogen atom or phenyl, R 23And R 33Be respectively C 1-6Alkyl, C 1-6Haloalkyl or C 3-10Cycloalkyl,
R 43For
C can be selected from 3-10Cycloalkyl and C 1-6The C that the group of alkoxyl replaces 1-10Alkyl; Perhaps
C 1-6Haloalkyl,
R 53For
C 1-6Alkoxyl;
C 1-6Alkoxy C 1-6Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl, C 2-6Alkoxy carbonyl, " C can be selected from 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group or aryloxy group, heterocyclic group, C 1-6Alkanoyloxy, aralkoxy and C 1-6The C that 1～3 group in the alkylthio group replaces 1-10Alkyl or C 2-6Thiazolinyl; Perhaps
The group of formula (II-3) expression,
B is the group of aryl, furyl, thienyl, pyrazolyl, different  azoles base, pyridine radicals, formula (III) expression or the group of formula (IV-3) expression.
50. group with imine moiety as claimed in claim 49 or its officinal salt, W is-CO-.
51. group with imine moiety as claimed in claim 50 or its officinal salt,
X 3Be C (R 13),
R 53For
C 1-10Alkoxyl;
C 1-6Haloalkyl;
C can be selected from 1-6Alkoxyl, C 3-10Cycloalkyl and can be selected from " C 1-6Alkoxyl and halogen atom " the aryl that replaces of 1～5 group in the C that replaces of 1～3 group 1-10Alkyl; Perhaps
The group of formula (II-3) expression, B is a phenyl.
52. group with imine moiety as claimed in claim 51 or its officinal salt,
R 553For
Halogen atom;
C 1-10Alkyl;
C 1-6Haloalkyl;
C 1-10Alkoxyl;
C 1-6Halogenated alkoxy;
Can be by the aryl of 1～3 halogen atom replacement;
The aryloxy group that can be replaced by halogen atom;
Formula-N (R 633) R 733(in the formula, R 633And R 733Represent hydrogen atom or C respectively 1-6Alkyl) Biao Shi group;
Cyano group;
Nitro; Perhaps
C 2-6Alkoxy carbonyl,
R 563For
Hydrogen atom;
Halogen atom;
C 1-10Alkyl; Perhaps
C 1-6Haloalkyl,
R 573For
Hydrogen atom;
C 1-10Alkyl;
Halogen atom; Perhaps
C 1-10Alkoxyl.
53. group with imine moiety as claimed in claim 52 or its officinal salt, R 43Be C 3-10The C of cycloalkyl substituted 1-10Alkyl.
54. group with imine moiety as claimed in claim 49 or its officinal salt, X 3Be sulphur atom, W is-CO-or-SO 2-.
55. group with imine moiety as claimed in claim 54 or its officinal salt, R 23Be C 1-6Alkyl, R 43Be C 3-10The C of cycloalkyl substituted 1-10Alkyl, R 53Be the group of formula (II-3) expression, B is an aryl, R 553Be C 1-6Haloalkyl, R 563Be hydrogen atom, halogen atom, C 1-10Alkyl or C 1-10Alkoxyl, R 573Be hydrogen atom.
56. as each described group with imine moiety or its officinal salt in the claim 50～55, in formula (I-3), the spatial configuration of two keys of group shown in the＞C=N-CO-is (Z) configuration.
CNA2005800390054A 2004-11-15 2005-10-31 Imine compound Pending CN101065125A (en)

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JP162163/2005 2005-06-02
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102448957A (en) * 2009-03-27 2012-05-09 雅培制药有限公司 Compounds as cannabinoid receptor ligands
CN105579446A (en) * 2013-09-19 2016-05-11 巴斯夫欧洲公司 N-acylimino heterocyclic compounds
CN106117132A (en) * 2011-08-26 2016-11-16 明治制果药业株式会社 The autofrettage of noxious organism control agent

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102448957A (en) * 2009-03-27 2012-05-09 雅培制药有限公司 Compounds as cannabinoid receptor ligands
CN106117132A (en) * 2011-08-26 2016-11-16 明治制果药业株式会社 The autofrettage of noxious organism control agent
CN106117132B (en) * 2011-08-26 2018-11-09 明治制果药业株式会社 The autofrettage of noxious organism control agent
CN105579446A (en) * 2013-09-19 2016-05-11 巴斯夫欧洲公司 N-acylimino heterocyclic compounds
US10206397B2 (en) 2013-09-19 2019-02-19 Basf Se N-acylimino heterocyclic compounds
US10757938B2 (en) 2013-09-19 2020-09-01 Basf Se N-acylimino Heterocyclic Compounds

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